Cited by 634Genetics and Neurodevelopmental DisordersAutism Spectrum Disorder ResearchGenomic variations and chromosomal abnormalities

The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index; none of the 37 sources its claims cite is checked for support yet.

Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments

Open access

Leblond, Claire S., Nava, Caroline, Polge, Anne, Gauthier, Julie, Huguet, Guillaume, Lumbroso, Serge, Giuliano, Fabienne, Stordeur, Coline, Depienne, Christel, Mouzat, Kevin, Pinto, Dalila, Howe, Jennifer, Lemière, Nathalie, Durand, Christelle M., Guibert, Jessica, Ey, Elodie, Toro, Roberto, Peyre, Hugo, Mathieu, Alexandre, Amsellem, Frédérique, Rastam, Maria, Gillberg, I. Carina, Rappold, Gudrun A., Holt, Richard, Monaco, Anthony P., Maestrini, Elena, Galan, Pilar, Heron, Delphine, Jacquette, Aurélia, Afenjar, Alexandra, Rastetter, Agnès, Brice, Alexis, Devillard, Françoise, Assouline, Brigitte, Laffargue, Fanny, Lespinasse, James, Chiesa, Jean, Rivier, François, Bonneau, Dominique, Regnault, Beatrice, Zelenika, Diana, Delepine, Marc, Lathrop, Mark, Sanlaville, Damien, Schluth-Bolard, Caroline, Edery, Patrick, Perrin, Laurence, Tabet, Anne Claude, Schmeisser, Michael J., Boeckers, Tobias M., Coleman, Mary, Sato, Daisuke, Szatmari, Peter, Scherer, Stephen W., Rouleau, Guy A., Betancur, Catalina, Leboyer, Marion, Gillberg, Christopher, Delorme, Richard, Bourgeron, Thomas·2014·PLoS Genetics

DOI 10.1371/journal.pgen.1004580PMC PMC4154644

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Abstract

SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice.

AI snapshot

Written from the paper’s full text.

TL;DR

This meta-analysis plus new screening found SHANK copy-number and truncating coding-sequence variants in ~1% of patients with ASD, with a gene-specific gradient of cognitive severity: SHANK1 in normal-IQ autism, SHANK2 in mild ID, and SHANK3 in moderate-to-profound ID. SHANK3 mutations were the most frequent and clinically relevant, accounting for more than 1 in 50 cases with ASD plus intellectual disability.

Key findings

SHANK1 mutations were rare: CNVs in 0.04% of ASD cases (2/5,657) versus 0/19,163 controls (meta-analysis fixed-effect P=0.19, OR=2.73, 95% CI 0.60–12.48), and no truncating coding-sequence variants were found (0/760 ASD, 0/492 controls). Damaging missense variants were more frequent in ASD (3.16% vs 1.02%, P=0.012, OR=3.17), but this did not survive Bonferroni correction; carriers had normal IQ (mean IQ=107) and ASD.
SHANK2 mutations were associated with mild ID: CNVs in 0.05% of ASD cases (3/5,657) versus 0/19,163 controls (P=0.076, OR=3.76), truncating coding-sequence variants in 0.12% (1/851 ASD vs 0/1,090 controls), and damaging missense variants in 4.58% vs 2.66% (P=0.025, OR=1.76). Carriers had mild to moderate ID (mean IQ=62±17).
SHANK3 mutations were most frequent and severe: CNVs in 0.18% of ASD cases (10/5,657) versus 0.01% of controls (2/19,163; P=0.019, OR=4.05), and truncating coding-sequence variants in 0.51% (11/2,147 ASD vs 0/1,031 controls; P=0.29, OR=2.85). In ASD with ID (IQ<70), de novo or truncating SHANK3 mutations reached 2.12% (CNVs 6/917=0.65%; coding-sequence 9/611=1.47%), versus 0% in ASD without ID and 0.01% in controls; carriers had moderate to severe/profound ID (mean IQ=31±8).
Across genes, truncating/CNV mutations were present in ~1% of ASD cases: SHANK1 0.04%, SHANK2 0.17%, SHANK3 0.69%, with a gradient from normal IQ (SHANK1) to mild ID (SHANK2) to moderate-to-profound ID (SHANK3).

Methods

Meta-analysis of SHANK copy-number variants (5,657 ASD cases and 19,163 controls from 11 studies, including this one) and coding-sequence variants (760–2,147 ASD cases and 492–1,090 controls depending on gene, from 10 studies, including this one). New screening included 46 ASD cases/454 controls for CNVs, 251 ASD cases/492 controls for SHANK1 exons, and 429 ASD cases/80 controls added to SHANK3 coding-sequence screening; de novo or truncating mutation carriers underwent extended clinical investigation.
ASD diagnosis used ADI-R, and in some cases ADOS or DISCO-10; IQ was measured with age-appropriate Wechsler scales, Raven’s Standard Progressive Matrices, or PPVT, plus systematic physical examination for dysmorphic and neurological features.
Statistical analysis used two-sided Fisher’s exact tests, Bonferroni correction for 12 tests (corrected α=0.0042), inverse-variance fixed- and random-effects meta-analysis, heterogeneity statistics (Q, I², Tau²), and power calculations; SHANK2 and SHANK3 reference sequences were corrected before screening.

Limitations

The paper states that inherited SHANK1 and SHANK2 variant associations did not survive Bonferroni correction, and the study was underpowered for low-effect-size inherited variants: power to detect an OR of 1.5 for SHANK1, SHANK2, and SHANK3 missense inherited damaging variants was 8%, 34%, and 17%, respectively; larger IQ-stratified cohorts are needed.
The paper notes that only non-synonymous mutations in known exons were screened; splicing isoforms, synonymous mutations, and regulatory variants were rarely reported, and whole-exome sequencing studies were excluded because of very low SHANK3 coverage. Some father DNA was unavailable for two SHANK3 truncating cases, two SHANK2 deletion patients were not included in prevalence calculations because the exact number screened was unavailable, and two unvalidated SHANK3 control deletions should be interpreted with caution.
Evident from the text: the meta-analysis relied on combining heterogeneous published cohorts, and although the authors contacted corresponding authors to avoid overlapping samples, control data for SHANK1 coding variants were incomplete in one prior study and were excluded from that analysis.

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Registry

Crossref · 10.1371/journal.pgen.1004580

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 37 cited sources checked · 0 supported · 0 flagged

A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we observed rare coding-sequence variants predicted as damaging in 4.58% of the patients with ASD compared with 2.66% of the controls (Fisher's exact test two-sided, P = 0.025, OR = 1.76, 95% CI = 1.05–2.97).”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK2 in ASD
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Rests on an assumption: Rare coding-sequence variants predicted as damaging by polyphen-2 are functionally deleterious.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The individuals carrying a SHANK2 de novo deletion were diagnosed with autistic disorder or pervasive developmental disorder not otherwise specified (PDD-NOS) in combination with mild to moderate ID (mean IQ = 62±17)”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK2 in ASD
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Rests on an assumption: Patients carrying de novo or truncating SHANK mutations who underwent clinical investigation are representative of all individuals with such mutations.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to prof”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Abstract
Load-bearingStrength:plain· not yet calibratedn = 5,657
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Rests on an assumption: The published studies included in the meta-analysis used comparable methods for detecting SHANK variants and comparable ASD/control ascertainment.
In the paper
“In the Canadian family, the elder sister carrying the SHANK3 duplication was diagnosed with attention-deficit/hyperactivity disorder (ADHD) and developmental delay [13].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK3 in ASD
What the sources say
- Not checked yetcites [13] R Moessner, 2007, Contribution of SHANK3 mutations to autism spectrum disorder, Am J Hum Genet source
Strength:plain· not yet calibratedSingle case
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes

Show all 56 claims

Probably not a substantial claim. 26
It may state two separate claims as one. 26
The quote only partly states this claim. 2

A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“They also displayed minor signs of dysmorphism (broad nasal bridge, thin upper lip, pointed chin, clinodactyly) and abnormal neurological examination (Table 2).”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK2 in ASD
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: Patients carrying de novo or truncating SHANK mutations who underwent clinical investigation are representative of all individuals with such mutations.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“They displayed early signs of developmental delay, mild motor delay and significant language delay.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK2 in ASD
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: Patients carrying de novo or truncating SHANK mutations who underwent clinical investigation are representative of all individuals with such mutations.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism”
- Also stated in: § SHANK1 in ASD · plain
  “deletions disrupting SHANK1 were detected in 0.04% (n = 2/5 657) of patients with ASD and were never found in 19 163 controls (Meta-analysis – Inverse variance method - fixed effect model P = 0.19, OR = 2.73, 95% CI = 0.60–12.48)”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Abstract
Load-bearingStrength:plain· not yet calibratedn = 2
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In three families from France and Canada, the SHANK3 deletions originated from a balanced translocation present in a healthy parent [6], [13].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK3 in ASD
What the sources say
- Not checked yetcites [6] CM Durand, 2007, Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders, Nat Genet source
- Not checked yetcites [13] R Moessner, 2007, Contribution of SHANK3 mutations to autism spectrum disorder, Am J Hum Genet source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedn = 3
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, in two families, a sibling carried the reciprocal SHANK3 duplication.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK3 in ASD
What the sources say
- Not checked yetcites [6] CM Durand, 2007, Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders, Nat Genet source
- Not checked yetcites [13] R Moessner, 2007, Contribution of SHANK3 mutations to autism spectrum disorder, Am J Hum Genet source
Strength:plain· not yet calibratedn = 2
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mutations of the SHANK genes were detected in the whole spectrum of ASD with a gradient of severity in cognitive impairment.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Discussion
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The cohorts included in the meta-analysis are representative of the whole ASD population.
In the paper
“Interestingly, sex differences might modulate the phenotype since females carrying an inherited SHANK1 deletion exhibited anxiety and shyness, but did not fulfill criteria for ASD [19].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > SHANK1 in ASD
What the sources say
- Not checked yetcites [19] D Sato, 2012, SHANK1 Deletions in Males with Autism Spectrum Disorder, Am J Hum Genet source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment.”
- Also stated in: § Cohorts used for the meta-analysis of SHANK mutations · plain
  “Mutations in SHANK1-3 are associated with a gradient of severity in cognitive impairment.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Abstract
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibratedn = 5,657
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The clinical phenotype associated with SHANK mutations is primarily attributable to the SHANK gene affected rather than to other genetic or environmental factors.
In the paper
“Here, we focused on the three SHANK genes, which code for large synaptic scaffold proteins of the post-synaptic density [12].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Introduction
What the sources say
- Not checked yetcites [12] AM Grabrucker, 2011, Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies, Trends Cell Biol source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“male individuals carrying SHANK1 deletions do not present with language delay or ID and are diagnosed with normal IQ ASD or Asperger syndrome [19].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Discussion
What the sources say
- Not checked yetcites [19] D Sato, 2012, SHANK1 Deletions in Males with Autism Spectrum Disorder, Am J Hum Genet source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Previous functional studies have shown that inherited variants are associated with a statistically significant reduction in the density of synapses, although not as severe as the reduction caused by the de novo or truncating mutations [6], [18], [42]–[44].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Discussion
What the sources say
- Not checked yetcites [6] CM Durand, 2007, Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders, Nat Genet source
- Not checked yetcites [18] CS Leblond, 2012, Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders, PLoS Genet source
- Not checked yetcites [42]–[44]
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“The two SHANK3 deletions reported by Glessner et al. (2009) [34] in control subjects have not been validated and should be interpreted with caution.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > Cohorts used for the meta-analysis of SHANK mutations
What the sources say
- Not checked yetcites [34] JT Glessner, 2009, Autism genome-wide copy number variation reveals ubiquitin and neuronal genes, Nature source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, our genetic and clinical findings provide additional support for considering SHANK mutations in a broad spectrum of patients with ASD.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Discussion
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim. It may be too vague to check against evidence.
- Rests on an assumption: The cohorts included in the meta-analysis are representative of the whole ASD population.
In the paper
“It has been proposed that abnormal SHANK levels at the synapse might result in the mislocalization, de-clustering and/or functional impairment of several other crucial synaptic proteins such as cytoskeletal regulators and/or neurotransmitter receptors [12] (Table 3).”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Discussion
What the sources say
- Not checked yetcites [12] AM Grabrucker, 2011, Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies, Trends Cell Biol source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“For SHANK1, there are two studies (Sato et al. (2012) [19] and this study), but Sato et al. (2012) [19] did not screen for all SHANK1 exons in the controls. Therefore these controls were not included here.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Results > Cohorts used for the meta-analysis of SHANK mutations
What the sources say
- Not checked yetcites [19] D Sato, 2012, SHANK1 Deletions in Males with Autism Spectrum Disorder, Am J Hum Genet source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“other genes involved in the same synaptic pathway, including neurexin and neuroligin genes, appear to be associated with a variety of neuropsychiatric disorders [11].”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Discussion
What the sources say
- Not checked yetcites [11] TC Sudhof, 2008, Neuroligins and neurexins link synaptic function to cognitive disease, Nature source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“For controls, the two SHANK3 deletions reported by Glessner et al. (2009) among 2 519 individuals, were not validated and thus should be regarded with caution.”
§ Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments > Materials and Methods > SHANK copy-number and coding-sequence variants in ASD
What the sources say
- Not checked yetcites Glessner et al. (2009) source
Strength:plain· not yet calibratedn = 2,519
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.

53 of 53

The paper relies on this without support.
The published studies included in the meta-analysis used comparable methods for detecting SHANK variants and comparable ASD/control ascertainment.
“This meta-analysis included the published data from 14 studies in addition to a new screening of SHANK copy-number variants and coding sequence variants.”
The paper relies on this without support.
Rare coding-sequence variants predicted as damaging by polyphen-2 are functionally deleterious.
“rare inherited coding-sequence variants predicted as damaging were, however, more frequent in patients with ASD than in controls”
The paper relies on this without support.
The clinical phenotype associated with SHANK mutations is primarily attributable to the SHANK gene affected rather than to other genetic or environmental factors.
“Mutations in SHANK1-3 are associated with a gradient of severity in cognitive impairment.”
The paper relies on this without support.
Patients carrying de novo or truncating SHANK mutations who underwent clinical investigation are representative of all individuals with such mutations.
“When possible, the patients carrying truncating mutations altering SHANK genes underwent further clinical investigations (Table 2 & S7).”
The paper relies on this without support.
The cohorts included in the meta-analysis are representative of the whole ASD population.
“In the whole spectrum of ASD, we estimated that 0.04%, 0.17% and 0.69% of cases with ASD had heterozygous truncating mutations in SHANK1, SHANK2 or SHANK3, respectively (Table 1).”
The paper relies on this without support.
The control groups included in the meta-analysis are representative of the general population without ASD.
“0.01% in controls”
The paper relies on this without support.
The SHANK mutations classified as truncating or damaging are pathogenic.
“we estimated that 0.04%, 0.17% and 0.69% of cases with ASD had heterozygous truncating mutations in SHANK1, SHANK2 or SHANK3, respectively (Table 1).”

7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139 · cited 1×
“The Q statistic is a chisquare test for heterogeneity, and the I(2) and Tau(2) are the proportion of observed variance in effect sizes across studies for fixed effect model and random effect model, respectively [55].”
Method
Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders
Lord, C., Rutter, M., & Le Couteur, A. (1994) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02172145 · Cited by 9,065 · cited 4×
“In Sweden, in few cases, the Diagnostic Interview for Social and Communication Disorders (DISCO-10) [50] was used instead of the ADI-R.”
MethodInfluential
The Autism Diagnostic Observation Schedule—Generic: A Standard Measure of Social and Communication Deficits Associated with the Spectrum of Autism
Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Leventhal, B. L., DiLavore, P. C., Pickles, A., & Rutter, M. (2000) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1005592401947 · Cited by 7,520 · cited 1×
“The autism-spectrum diagnosis was based on the Autism Diagnostic Interview – Revised (ADI-R) [48] and for some of the patients, the Autism Diagnostic Observation Schedule (ADOS) [49].”
Method
THE USE OF CONFIDENCE OR FIDUCIAL LIMITS ILLUSTRATED IN THE CASE OF THE BINOMIAL
Clopper, C. J., & Pearson, E. S. (1934) · Biometrika · doi:10.1093/biomet/26.4.404 · Cited by 5,327 · cited 1×
“Prevalence and confidence intervals of single studies were evaluated using Clopper and Pearson method [54].”
Method
Strong association of de novo copy number mutations with autism
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., et al. (2007) · Science · doi:10.1126/science.1138659 · Cited by 2,795 · cited 1×
“For the second patient AUN_007, the deletion covers the exon 22 of SHANK3 and exons 1 to 3 of ACR .”
Background
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
O’Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., et al. (2012) · Nature · doi:10.1038/nature10989 · Cited by 2,165 · cited 1×
“[32,36,37] and no truncating coding-sequence variation within SHANK1 and SHANK3.”
Background
De novo mutations revealed by whole-exome sequencing are strongly associated with autism
Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., Ercan-Sencicek, A. G., DiLullo, N. M., Parikshak, N. N., Stein, J. L., et al. (2012) · Nature · doi:10.1038/nature10945 · Cited by 2,084 · cited 2×
“[32,36,37] and no truncating coding-sequence variation within SHANK1 and SHANK3.”
BackgroundResult
Functional impact of global rare copy number variation in autism spectrum disorders
Pinto, D., Pagnamenta, A. T., Klei, L., Anney, R., Merico, D., Regan, R., Conroy, J., Magalhaes, T. R., Correia, C., Abrahams, B. S., et al. (2010) · Nature · doi:10.1038/nature09146 · Cited by 2,013 · cited 2×
“SHANK copy-number and coding-sequence variants in ASD SHANK copy-number variants were detected with the Illumina Human 1M-Duo BeadChip, and validated by quantitative PCR as previously described [8,18].”
MethodSelf-citation
Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism
Study, P. A. R. I. S., Jamain, S., Quach, H., Betancur, C., Råstam, M., Colineaux, C., Gillberg, I. C., Soderstrom, H., Giros, B., Leboyer, M., et al. (2003) · Nature Genetics · doi:10.1038/ng1136 · Cited by 1,851 · cited 1×
“In particular, mutations in genes coding for synaptic cell adhesion molecules and scaffold proteins — such as neuroligins, neurexins and SHANK — have been repeatedly reported in individuals with ASD [5–10].”
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Neuroligins and neurexins link synaptic function to cognitive disease
Südhof, T. C. (2008) · Nature · doi:10.1038/nature07456 · Cited by 1,849 · cited 2×
“These proteins play a crucial role in the formation and stabilization of synapses [11,12].”
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Identification of the common neurobiological process disturbed in genetic and non-genetic models for autism spectrum disorders
Malijauskaite, S., Sauer, A. K., Hickey, S., Franzoni, M., Grabrucker, A. M., & McGourty, K. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04617-3 · Cited by 8
Evidence for parent-of-origin effects in autism spectrum disorder: a narrative review
Ryan, N., & Heron, E. A. (2023) · Journal of Applied Genetics · doi:10.1007/s13353-022-00742-8 · Cited by 8
Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes
Lu, X., Ni, P., Suárez-Meade, P., Ma, Y., Forrest, E., Wang, G., Wang, Y., Quiñones‐Hinojosa, A., Gerstein, M., & Jiang, Y.-H. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114376 · Cited by 10
Copy number variations of SHANK3 and related sensory profiles in Egyptian children with autism spectrum disorder
Meguid, N. A., Eid, O. M., Reda, M., Elalfy, D. Y., & Hussein, F. (2020) · Research in Autism · doi:10.1016/j.rasd.2020.101558 · Cited by 8
Dystrophin genetic variants and autism
Passos‐Bueno, M. R., Costa, C. I. S., & Zatz, M. (2022) · Discover Mental Health · doi:10.1007/s44192-022-00008-z · Cited by 11
Descriptive Analysis of Adaptive Behavior in Phelan–McDermid Syndrome and Autism Spectrum Disorder
Serrada-Tejeda, S., Martínez-Piédrola, R. M., Máximo-Bocanegra, N., Sánchez-Herrera-Baeza, P., & Pérez‐de‐Heredia‐Torres, M. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.893003 · Cited by 8
Autism Spectrum Disorder
Saxena, A., & Chahrour, M. H. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-800685-6.00016-3 · Cited by 10
Enhanced Glutamatergic Currents at Birth in Shank3 KO Mice
Chiesa, M., Nardou, R., Lozovaya, N., Eftekhari, S., Tyzio, R., Guimond, D., Ferrari, D. C., & Ben‐Ari, Y. (2019) · Neural Plasticity · doi:10.1155/2019/2382639 · Cited by 9
Restoring Glutamate receptosome dynamics at synapses rescues Autism-like deficits in Shank3-deficient micePreprint
Moutin, E., Sakkaki, S., Compan, V., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.30.424827 · Cited by 8
Cromosoma 22 en anillo en paciente con trastorno del neurodesarrollo
Mendoza, P., Huertas-Pérez, G., Rosales, L. M., & Rosado, L. A. M. (2023) · Salud Ciencia y Tecnología - Serie de Conferencias · doi:10.56294/sctconf2023345 · Cited by 7
Cancer drug repurposing in autism spectrum disorder
Pedini, G., Chen, C., Achsel, T., & Bagni, C. (2023) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2023.09.008 · Cited by 7
Association of genetic variants with autism spectrum disorder in Japanese children revealed by targeted sequencing
Shiota, Y., Nishiyama, T., Yokoyama, S., Yoshimura, Y., Hasegawa, C., Tanaka, S., Iwasaki, S., & Kikuchi, M. (2024) · Frontiers in Genetics · doi:10.3389/fgene.2024.1352480 · Cited by 7
Phenome-wide profiling identifies genotype-phenotype associations in Phelan-McDermid syndrome using family-sourced data from an international registry
Yin, R., Wack, M., Hassen‐Khodja, C., McDuffie, M. T., Bliss, G., Horn, E. J., Kothari, C. R., McLarney, B., Davis, R., Hanson, K., et al. (2024) · Molecular Autism · doi:10.1186/s13229-024-00619-z · Cited by 11
Self-citation
Role of Odor Novelty on Olfactory Issues in Autism Spectrum Disorder
Scheier, Z. A., Sturm, K. L., Colavecchio, J. A., Pradhan, A., & Otazu, G. H. (2024) · Genes Brain & Behavior · doi:10.1111/gbb.70008 · Cited by 6
Large 22q13.3 deletions perturb peripheral transcriptomic and metabolomic profiles in Phelan-McDermid syndrome
Breen, M. S., Fan, X., Levy, T., Pollak, R. M., Collins, B. L., Osman, A., Tocheva, A. S., Şahin, M., Berry‐Kravis, E., Soorya, L. V., et al. (2022) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2022.100145 · Cited by 7
Head Size in Phelan–McDermid Syndrome: A Literature Review and Pooled Analysis of 198 Patients Identifies Candidate Genes on 22q13
Sarasua, S. M., DeLuca, J. M., Rogers, C. R., Phelan, K., Rennert, L., Powder, K. E., Weisensee, K. E., & Boccuto, L. (2023) · Genes · doi:10.3390/genes14030540 · Cited by 8
Autism Spectrum Disorder: The Cerebellum, Genes, and Pathways
D’Mello, S. R. (2025) · Neurology International · doi:10.3390/neurolint17100173 · Cited by 15
Hypersynchronous iPSC-derived SHANK2 neuronal networks are rescued by mGluR5 agonism
McCready, F. P., Pradeepan, K. S., Khaki, M., Wei, W., Guevara‐Ferrer, M., Matusiak, N., Feng, B., Piekna, A., Martínez-Trujillo, J., & Ellis, J. (2025) · Stem Cell Reports · doi:10.1016/j.stemcr.2025.102718 · Cited by 7
Applications of PET and SPECT in Patients with Autism Spectrum Disorder
Martini, A. L., Quartuccio, N., Schiera, I. G., Berti, V., Burroni, L., & Cistaro, A. (2023) · Current Medical Imaging Formerly Current Medical Imaging Reviews · doi:10.2174/0115734056232408230927072959 · Cited by 6
Identification of Neurotransmission and Synaptic Biological Processes Disrupted in Autism Spectrum Disorder Using Interaction Networks and Community Detection Analysis
Vilela, J. E. R., Martiniano, H., Marques, A. R., Santos, J. X., Asif, M., Rasga, C., Oliveira, G., & Vicente, A. M. (2023) · Biomedicines · doi:10.3390/biomedicines11112971 · Cited by 7
Gastrointestinal Dysfunction in Genetically Defined Neurodevelopmental Disorders
Davidson, E. A., Holingue, C., Jiménez-Gómez, A., Dallman, J. E., & Moshiree, B. (2023) · Seminars in Neurology · doi:10.1055/s-0043-1771460 · Cited by 6
Hyperthermia elevates brain temperature and improves behavioural signs in animal models of autism spectrum disorder
López-Rodríguez, A. B., Murray, C., Kealy, J., Towns, C., Nazmi, A., Arnold, L., Doran, M. M., Lowry, J., & Cunningham, C. M. (2023) · Molecular Autism · doi:10.1186/s13229-023-00569-y · Cited by 7
Pharmacological modulation of developmental and synaptic phenotypes in human SHANK3 deficient stem cell-derived neuronal models
Thibaudeau, A., Schmitt, K., François, L., Chatrousse, L., Hoffmann, D., Cousin, L., Weiss, A., Vuidel, A., Jacob, C. B., Sommer, P., et al. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02947-3 · Cited by 9
SHANK Mutations in Intellectual Disability and Autism Spectrum Disorder
Schmeißer, M. J., & Verpelli, C. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800109-7.00010-8 · Cited by 7
Burden of Rare Copy Number Variants in Microcephaly: A Brazilian Cohort of 185 Microcephalic Patients and Review of the Literature
Tolezano, G. C., Bastos, G. C., da Costa, S. S., Freire, B. L., Homma, T. K., Honjo, R. S., Yamamoto, G. L., Passos‐Bueno, M. R., Koiffmann, C. P., Kim, C. A., et al. (2022) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-022-05853-z · Cited by 7
Predictive neural processing in adult zebrafish depends on shank3bPreprint
Huang, K., Rupprecht, P., Schebesta, M., Serluca, F. C., Kitamura, K., Bouwmeester, T., & Friedrich, R. W. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/546457 · Cited by 5
Progress in magnetic resonance imaging of autism model mice brain
Yang, D., Zhao, Y., Nie, B., An, L., Wan, X., Wang, Y., Wang, W., Cai, G., & Wu, S. (2022) · Wiley Interdisciplinary Reviews Cognitive Science · doi:10.1002/wcs.1616 · Cited by 5
Protein-truncating variants and deletions of SHANK2 are associated with autism spectrum disorder and other neurodevelopmental concerns
Silver, H., Greenberg, R., Siper, P. M., Zweifach, J., Soufer, R., Şahin, M., Berry‐Kravis, E., Soorya, L. V., Thurm, A., Bernstein, J. A., et al. (2025) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-025-09600-0 · Cited by 4
Increased Radiation Sensitivity in Patients with Phelan-McDermid Syndrome
Jesse, S., Kuhlmann, L., Hildebrand, L. S., Magelssen, H., Schmaus, M., Timmermann, B., Andres, S., Fietkau, R., & Distel, L. V. (2023) · Cells · doi:10.3390/cells12050820 · Cited by 5
The Genetic and Epigenetic Basis Involved in the Pathophysiology of ASD: Therapeutic Implications
Carrascosa-Romero, M. C., & de Cabo, C. (2017) · InTech eBooks · doi:10.5772/66854 · Cited by 5
Behavioral Deficits in Adolescent Mice after Sub-Chronic Administration of NMDA during Early Stage of Postnatal Development
Adil, K. J., Remonde, C. G., Gonzales, E. L., Boo, K.-J., Kwon, K. J., Kim, D. H., Kim, H. J., Cheong, J. H., Shin, C. Y., & Jeon, S. J. (2022) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2021.194 · Cited by 4
11q13.3q13.4 deletion plus 9q21.13q21.33 duplication in an affected girl arising from a familial four‐way balanced chromosomal translocation
Zhang, Q., Wang, Y., Zhou, J., Zhou, R., Liu, A., Meng, L., Ji, X., Hu, P., & Xu, Z. (2023) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.2248 · Cited by 4
Identification of novel SHANK2 variants in two Chinese families via exome and RNA sequencing
Wu, Y., Li, W., Tan, B., & Luo, S. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1275421 · Cited by 5
Hyperexcitability and translational phenotypes in a preclinical model of SYNGAP1 mutationsPreprint
Fenton, T. A., Haouchine, O. Y., Hallam, E. L., Smith, E. M., Jackson, K. C., Rahbarian, D., Canales, C. P., Adhikari, A., Nord, A. S., Ben‐Shalom, R., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.24.550093 · Cited by 4
Disease-linked mutations dysregulate neuronal condensate physical properties, composition, and RNA translationPreprint
Liyanage, L. A., McCready, F. P., Chung, S., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.01.621623 · Cited by 5
Genetic changes linked to two different syndromic forms of autism enhance reinforcement learning in early adolescent male but not female micePreprint
Chase, J. B., Li, J., Lin, W. C., Tai, L.-H., Castro, F., Collins, A. G. E., & Wilbrecht, L. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.15.633099 · Cited by 5
An X-linked long non-coding RNA, PTCHD1-AS, and the core features of autism
Bradley, C. A., Ko, S. Y., Tian, M., Ralph, L. T., D’Abate, L., Lee, J., Liu, T., Wang, J., Tidball, P., de Aquino, M. M., et al. (2026) · Nature · doi:10.1038/s41586-026-10515-6 · Cited by 5
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Neural connections and molecular mechanisms underlying motor skill deficits in genetic models of autism spectrum disorders
Duan, J., Zeng, D., Wu, T., Luo, Z., Jingwen, G., Tan, W., & Zeng, Y. (2025) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2025.102759 · Cited by 4
A Frank Assessment of SHANK : Impacts of Pathogenic Variations in SHANK3 on Preclinical Models of Phelan McDermid Syndrome
Lin, V., Matta, S. M., Dallman, J. E., Hosie, S., Moreau, M., Franks, A. E., Bourgeron, T., & Hill‐Yardin, E. L. (2025) · Autism Research · doi:10.1002/aur.70112 · Cited by 5
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The Shank3Venus/Venus knock in mouse enables isoform-specific functional studies of Shank3a
Bouquier, N., Sakkaki, S., Raynaud, F., Hemonnot-Girard, A.-L., Seube, V., Compan, V., Bertaso, F., Perroy, J., & Moutin, E. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1081010 · Cited by 3
De novo copy number variations in candidate genomic regions in patients of severe autism spectrum disorder in Vietnam
Bui, H. T. P., Do, D. H., Ly, H. T. T., Tran, K. T., Le, H. T. T., Nguyen, K. T., Pham, L. T. D., Le, H. D., Le, V. S., Mukhopadhyay, A., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0290936 · Cited by 4
The Effect of Parental Faecal Microbiome Transplantation from Children with Autism Spectrum Disorder on Behavior and Gastrointestinal Manifestations in the Male Offspring of Shank3 Mice
Borbélyová, V., Szabó, J., Sušienková, P., Potvin, J., Belvončíková, P., Groß, T., Jančovičová, A., Bačová, Z., Rašková, B., Szadvári, I., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26135927 · Cited by 5
Shank3 contributes to neuropathic pain by facilitating the SNI-dependent increase of HCN2 and the expression of PSD95
Zhang, X., Li, X., Wang, H., Xie, X., Li, Y., Xu, X., Su, S., Zhao, H., Li, J., Ke, C., et al. (2020) · Neuroscience Research · doi:10.1016/j.neures.2020.05.010 · Cited by 4
Case Report: Lennox–Gastaut Epileptic Encephalopathy Responsive to Cannabidiol Treatment Associated With a Novel de novo Mosaic SHANK1 Variant
Paprocka, J., Ziętkiewicz, S., Kosińska, J., Kaczorowska, E., & Płoski, R. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.735292 · Cited by 4
Genetic Analysis Implicates Dysregulation of SHANK2 in Renal Cell Carcinoma Progression
Chang, C., Huang, S., Hsueh, Y., Geng, J., Huang, C., & Bao, B. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph191912471 · Cited by 4
Downregulation of the Autism Spectrum Disorder Gene Shank2 Decreases Bone Mass in Male Mice
Ahmad, M., Stirmlinger, N., Jan, I., Stifel, U., Lee, S., Weingandt, M., Kelp, U., Bockmann, J., Ignatius, A. A., Böckers, T. M., et al. (2022) · JBMR Plus · doi:10.1002/jbm4.10711 · Cited by 4
Deficiency of SHANK3 isoforms impairs thermal hyperalgesia and dysregulates the expression of postsynaptic proteins in the spinal cord
Huang, M., Pu, S., Jiang, W., Worley, P. F., & Xu, T. (2020) · Neuroscience Research · doi:10.1016/j.neures.2020.03.001 · Cited by 4
Translational pediatrics: clinical perspective for Phelan–McDermid syndrome and autism research
Sakai, Y., Okuzono, S., Schaaf, C. P., & Ohga, S. (2021) · Pediatric Research · doi:10.1038/s41390-021-01806-x · Cited by 4
Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan McDermid syndrome and autismPreprint
Breen, M. S., Browne, A., Hoffman, G. E., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/855163 · Cited by 4
The pathogenic factor of ZC4H2-associated rare disorder is a postsynaptic regulator for synaptic activity and cognitive function
Wan, L. P., Li, Y., Zhao, S., Zhao, S., Song, N., Yuan, K., Yang, C., Ding, Y., Mao, B., Sheng, N., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2426375122 · Cited by 4
Structural Variations Identified in Patients with Autism Spectrum Disorder (ASD) in the Chinese Population: A Systematic Review of Case-Control Studies
Chair, S. Y., Chow, K. M., Chan, C. W.-L., Chan, J. Y., Law, B., & Waye, M. M. Y. (2024) · Genes · doi:10.3390/genes15081082 · Cited by 4
Disentangling the role of tau pathology in autism spectrum disorders
Villavicencio-Tejo, F., Olesen, M. A., Moya, M. L., & Quintanilla, R. A. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111496 · Cited by 4
SHANK Mutations May Disorder Brain Development
Poot, M. (2014) · Molecular Syndromology · doi:10.1159/000368949 · Cited by 3
SHANK3 Genotype Mediates Speech and Language Phenotypes in a Nonclinical Population
Manning, C., Hurd, P. L., Read, S., & Crespi, B. J. (2021) · Autism Research and Treatment · doi:10.1155/2021/6634584 · Cited by 3
Sex-specific modulation of safety learning in Shank2-deficient mice
Kreutzmann, J. C., Kahl, E., & Fendt, M. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.110973 · Cited by 4
Autism patient-derived SHANK2BY29X mutation affects the development of ALDH1A1 negative dopamine neuron
Lai, W., Zhao, Y., Chen, Y., Dai, Z., Chen, R., Niu, Y., Chen, X., Chen, S., Huang, G., Shan, Z., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02578-6 · Cited by 4
Simulated complexes formed from a set of postsynaptic proteins suggest a localised effect of a hypomorphic Shank mutation
Miski, M., Weber, Á., Fekete-Molnár, K., Keömley-Horváth, B. M., Csikász‐Nagy, A., & Gáspári, Z. (2024) · BMC Neuroscience · doi:10.1186/s12868-024-00880-1 · Cited by 4
Multiparametric Assays Capture Sex- and Environment-Dependent Modifiers of Behavioral Phenotypes in Autism Mouse Models
Wahl, L. F., Karim, A., Hassett, A. R., van der Doe, M., Dijkhuizen, S., & Badura, A. (2024) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2024.100366 · Cited by 3
MLPA analysis in a cohort of patients with autism
Peixoto, S., Melo, J. B., Ferrão, J., Pires, L. M., Lavoura, N., Pinto, M., Oliveira, G., & Carreira, I. M. (2017) · Molecular Cytogenetics · doi:10.1186/s13039-017-0302-z · Cited by 3
Neurobiology of Autism Spectrum Disorders
Martins, G. J. (2017) · Springer eBooks · doi:10.1007/978-3-319-42713-3_2 · Cited by 4
Shank3 mutations and HCN channelopathy: one size does not fit all
Monteiro, P. (2018) · The Journal of Physiology · doi:10.1113/jp275828 · Cited by 3
Pathogenic Variants and Ascertainment: Neuropsychiatric Disease Risk in a Health System Cohort
Banerjee, D., & Girirajan, S. (2023) · American Journal of Psychiatry · doi:10.1176/appi.ajp.20220934 · Cited by 3
Neuronal L-Type Calcium Channel Signaling to the Nucleus Requires a Novel CaMKIIα-Shank3 InteractionPreprint
Perfitt, T. L., Wang, X., Stephenson, J. R., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/551648 · Cited by 3
Author Correction: A framework to identify contributing genes in patients with Phelan-McDermid syndrome
Tabet, A., Rolland, T., Ducloy, M., Lévy, J., Buratti, J., Mathieu, A., Haye, D., Perrin, L., Dupont, C., Passemard, S., et al. (2019) · npj Genomic Medicine · doi:10.1038/s41525-019-0090-y · Cited by 3
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Autism associated SHANK3 missense point mutations impact conformational fluctuations and protein turnover at synapsesPreprint
Bucher, M., Niebling, S., Han, Y., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.31.424970 · Cited by 3
Identification of ultra-rare genetic variants in Pediatric Acute Onset Neuropsychiatric Syndrome (PANS) by exome and whole genome sequencingPreprint
Trifiletti, R. R., Lachman, H. M., Manusama, O. R., et al. (2021) · medRxiv · doi:10.1101/2021.05.25.21257256 · Cited by 3
Effect of Dietary Zinc Supplementation on the Gastrointestinal Microbiota and Host Gene Expression in the Shank3B-/- Mouse Model of Autism Spectrum DisorderPreprint
Wong, G. C., Jung, Y., Lee, K. C., Fourie, C., Handley, K. M., Montgomery, J. M., & Taylor, M. W. (2021) · Research Square · doi:10.21203/rs.3.rs-864668/v1 · Cited by 3
Juvenile Shank3 KO mice adopt distinct hunting strategies during prey capture learningPreprint
Kuhnle, C. G., Grimes, M., Casanova, V. M. S., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.13.495982 · Cited by 3
POSH undergoes phase separation and co-condensation with SHANK2/3 to regulate spine development
Yao, M., Yuan, L., Zheng, Y., & Xu, Z. (2025) · Protein & Cell · doi:10.1093/procel/pwaf066 · Cited by 2
Effect of dietary zinc supplementation on the gastrointestinal microbiome and host gene expression in the Shank3B−/− mouse model of autism spectrum disorder
Wong, G. C., Jung, Y., Lee, K., Fourie, C., Handley, K. M., Montgomery, J. M., & Taylor, M. W. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1607045 · Cited by 2
Tau Hypophosphorylation at Ser416 as the Early Molecular Imprint of Maternal Immune Activation: Insights from Female Mice Offspring
Bielska, E., Matuszewska, M., Wójcik, P., Wilkaniec, A., Cieślik, M., Gąssowska-Dobrowolska, M., Sulejczak, D., Czapski, G. A., & Adamczyk, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262110778 · Cited by 2
Uncovering the female phenotype in the VPA autism model: Brain-region specific synaptic pattern, microglial priming and behavioral singularity
Traetta, M. E., Codagnone, M. G., Litvak, E., Corpa, M. J. M., Uccelli, N. A., Zárate, S., & Reinés, A. G. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111591 · Cited by 2
Genetic analysis and reporting from whole-exome sequencing data in 1052 patients with intellectual disability
Pan, X., Qian, G., Liu, L., Zhang, X., Yang, Y., Zhang, Q., Tang, X., Yang, N., Dong, L., Yao, H., et al. (2026) · Journal of Molecular Medicine · doi:10.1007/s00109-026-02652-2 · Cited by 2
SHANK3 and beta-synuclein are novel blood-based biomarkers for the Phelan-McDermid syndrome: a pilot study
Pagano, J., Perez Arevalo, A., Nosanova, A., Bauer, H. F., Loth, E., Andres, S., Becker, F., Otto, M., Stefanoni, A., Verpelli, C., et al. (2026) · Translational Psychiatry · doi:10.1038/s41398-026-03932-8 · Cited by 2
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Inflammation increases the penetrance of behavioral impairment in Shank3 haploinsufficiency mice — can it explain the behavioral regression in Autism?
Qiao, S.-N., Wang, S. E., Kim, K.-Y., Jo, S., & Jiang, Y.-H. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03534-2 · Cited by 5
Zinc in Autism
Grabrucker, S., & Grabrucker, A. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804562-6.00009-9 · Cited by 4
Identification of primary copy number variations reveal enrichment of Calcium, and MAPK pathways sensitizing secondary sites for autism
Agarwala, S., Veerappa, A. M., & Ramachandra, N. B. (2020) · Egyptian Journal of Medical Human Genetics · doi:10.1186/s43042-020-00091-3 · Cited by 2
Implications of Genetic Factors and Modifiers in Autism Spectrum Disorders: a Systematic Review
Saleem, S., & Habib, S. H. (2022) · Review Journal of Autism and Developmental Disorders · doi:10.1007/s40489-022-00333-7 · Cited by 3
Neuropathological insights from SHANK3 mutant animal models
Zhang, J., He, D., & Li, X. (2023) · Ageing and Neurodegenerative Diseases · doi:10.20517/and.2023.18 · Cited by 3
Metataxonomic and Immunological Analysis of Feces from Children with or without Phelan–McDermid Syndrome
Alba, C., Herranz, C., Monroy, M. A., Aragón, A., Jurado, R., Díaz‐Regañón, D., Sánchez, C., Tolín, M., Miranda, C., Gómez-Taylor, B., et al. (2024) · Microorganisms · doi:10.3390/microorganisms12102006 · Cited by 2
Drug discovery strategy for TAK-418, a specific inhibitor of LSD1 enzyme activity, as a novel therapy for autism
Matsuda, S., Hattori, Y., & Kimura, H. (2024) · Advances in pharmacology · doi:10.1016/bs.apha.2024.10.017 · Cited by 2
Analyses of Human Genetic Data to Identify Clinically Relevant Domains of Neuroligins
Lehr, A. W., McDaniel, K. F., & Roche, K. W. (2024) · Genes · doi:10.3390/genes15121601 · Cited by 2
Determination of damaging SNP’s in SHANK3 gene with in silico methods
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Authors: Leblond, C. S., Nava, C., Polge, A., Gauthier, J., Huguet, G., Lumbroso, S., Giuliano, F., Stordeur, C., Depienne, C., Mouzat, K., Pinto, D., Howe, J., Lemière, N., Durand, C. M., Guibert, J., Ey, E., Toro, R., Peyre, H., Mathieu, A., Amsellem, F., Rastam, M., Gillberg, I. C., Rappold, G. A., Holt, R., Monaco, A. P., Maestrini, E., Galan, P., Heron, D., Jacquette, A., Afenjar, A., Rastetter, A., Brice, A., Devillard, F., Assouline, B., Laffargue, F., Lespinasse, J., Chiesa, J., Rivier, F., Bonneau, D., Regnault, B., Zelenika, D., Delepine, M., Lathrop, M., Sanlaville, D., Schluth-Bolard, C., Edery, P., Perrin, L., Tabet, A. C., Schmeisser, M. J., Boeckers, T. M., Coleman, M., Sato, D., Szatmari, P., Scherer, S. W., Rouleau, G. A., Betancur, C., Leboyer, M., Gillberg, C., Delorme, R., & Bourgeron, T.
Affiliations: Centre National de la Recherche Scientifique (FR)
Centre Hospitalier Universitaire de Nîmes (FR)
Centre Hospitalier Universitaire Sainte-Justine (CA)
Centre Hospitalier Universitaire de Nice (FR)
Icahn School of Medicine at Mount Sinai (US)
University of Toronto (CA)
Institut Pasteur (FR)
University of Gothenburg (SE)
Heidelberg University (DE)
Centre for Human Genetics (GB)
University of Bologna (IT)
Conservatoire National des Arts et Métiers (FR)
Assistance Publique – Hôpitaux de Paris (FR)
Hôpital Armand-Trousseau (FR)
Hôpital Couple Enfant (FR)
Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
Inserm (FR)
Lyon 1 Université (FR)
Universität Ulm (DE)
Montreal Neurological Institute and Hospital (CA)
University College London (GB)
Corresponding author: Bourgeron, Thomas
ORCID: Leblond, Claire S.
Nava, Caroline
Huguet, Guillaume
Lumbroso, Serge
Giuliano, Fabienne
Depienne, Christel
Pinto, Dalila
Durand, Christelle M.
Ey, Elodie
Toro, Roberto
Peyre, Hugo
Mathieu, Alexandre
Rappold, Gudrun A.
Monaco, Anthony P.
Maestrini, Elena
Galan, Pilar
Jacquette, Aurélia
Afenjar, Alexandra
Brice, Alexis
Laffargue, Fanny
Rivier, François
Bonneau, Dominique
Lathrop, Mark
Sanlaville, Damien
Edery, Patrick
Schmeisser, Michael J.
Boeckers, Tobias M.
Sato, Daisuke
Scherer, Stephen W.
Rouleau, Guy A.
Betancur, Catalina
Leboyer, Marion
Gillberg, Christopher
Delorme, Richard
Bourgeron, Thomas
Venue: PLoS Genetics
Publisher: Public Library of Science (PLoS)
Published: 2014-09-04
Volume: 10
Issue: 9
Pages: e1004580
ISSN: 1553-7390 (ISSN-L)
1553-7404
DOI: 10.1371/journal.pgen.1004580
PMC: PMC4154644
OpenAlex: W2141041915
Semantic Scholar: 765f93019a616c818b4b4525f202bb4aeb20152c
Cited by: 630
References: 58
Citations by year: 2026: 30 · 2025: 38 · 2024: 72 · 2023: 61 · 2022: 65 · 2021: 62 · 2020: 51 · 2019: 50 · 2018: 58 · 2017: 57 · 2016: 43 · 2015: 39 · 2014: 4
FWCI: 6.30
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS Genetics (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
HAL (submittedVersion, other-oa)
RePEc: Research Papers in Economics (submittedVersion)
Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
eScholarship@McGill (McGill) (submittedVersion)
Figshare (submittedVersion, cc-by)
Lund University Publications (Lund University) (submittedVersion, other-oa)
Funders: Fondation FondaMental
Fondation Cognacq-Jay
Fondation Orange
Deutsche Forschungsgemeinschaft
Agence Nationale de la Recherche (ANR-08-MNPS-0037)
Institut National de la Santé et de la Recherche Médicale
Centre National de la Recherche Scientifique
Université Paris Diderot
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords: autism spectrum disorder, SHANK3, Shank2, Shank1, copy number variation, truncating mutations, intellectual disability, cognitive impairment severity, de novo mutations, postsynaptic density, glutamatergic synapses, dendritic spines, mutation detection
MeSH terms: Child, Child Development Disorders, Pervasive, Cognition, Cognition Disorders, Female, Humans, Male, Intellectual Disability, Mutation, Nerve Tissue Proteins, Neurons, Synapses, Case-Control Studies, DNA Copy Number Variations

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Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments

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