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Cited by 356Genetics and Neurodevelopmental DisordersAutism Spectrum Disorder ResearchGenomics and Rare Diseases

A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP

Open access
Helsmoortel, Céline, Vulto-van Silfhout, Anneke T, Coe, Bradley P, Vandeweyer, Geert, Rooms, Liesbeth, van den Ende, Jenneke, Schuurs-Hoeijmakers, Janneke H M, Marcelis, Carlo L +17 more·2014·Nature Genetics
DOI 10.1038/ng.2899PMC PMC3990853
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Abstract

Despite the high heritability of autism spectrum disorders (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities, a genetic diagnosis can be established in only a minority of patients. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, as in Rett and fragile-X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in next-generation sequencing, for the large majority of cases no molecular diagnosis can be established. Here, we report ten patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD-associated genes known to date.

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Crossref · 10.1038/ng.2899

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 30 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Targeted screening of ADNP by molecular inversion probes or high-resolution melting in 2,891 patients with syndromic autism spectrum disorder identified four more mutation carriers.

    “Next, we targeted ADNP using molecular inversion probes (MIPs) or high resolution melt curve analysis (HRM) in a cohort of 2,891 patients with syndromic ASD and identified four more patients with mutations in this gene.”
    Quote in the paperSubstantial claim
  • Findingown data

    Mfold analysis showed that the clustered 4-bp deletions in patients 1, 6 and 8 lie in the stem of the same short hairpin.

    “Mfold analysis (web server for nucleic acid folding and hybridization prediction)27 showed that the clustered 4bp deletions of patients 1, 6 and 8 are located in the stem of the same short hairpin (Supplementary Fig. 2).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Zuker, M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 31, 3406–3415 (2003). source

      Not checked in the free run.

  • Findingown data

    The authors estimate that ADNP is mutated in at least 0.17% of autism spectrum disorder cases.

    “We estimate this gene to be mutated in at least 0.17% of ASD cases”
    • Also stated in: § Abstract · hedged
      “Mutations in ADNP may explain the etiology of 0.17% of patients with ASD (95% binomial confidence interval: 0.083% - 0.32%)”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The cohort of 5,776 patients screened is representative of the broader autism spectrum disorder population, so the observed ADNP mutation frequency can be used to estimate the proportion of autism spectrum disorder cases explained by ADNP.
  • Findingown data

    A wildtype-specific ADNP assay showed no difference from controls in patients 1, 6 and 8, indicating that the excess ADNP mRNA came from the mutant allele.

    “The expression of this ADNPwt amplicon was not different from controls, demonstrating that the excess ADNP mRNA in patients corresponds to the mRNA transcribed from the mutant allele.”
    Quote in the paperSubstantial claim
  • Findingown data

    The identified ADNP mutations cluster at specific positions.

    “Strikingly, the identified mutations appear to cluster at specific positions.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 18
  • May combine two claims. 24
  • The quote only partly states this claim. 1

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    A seizure disorder was observed in two patients.

    “A seizure disorder was noted in two patients.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    None of the ten ADNP mutations were found in the 1,000 Genomes Project, in 1,728 unaffected siblings from the Simons Simplex Collection screened by molecular inversion probes, or in 192 healthy Belgian control chromosomes analyzed by high-resolution melting.

    “None were present in the 1,000 Genomes Project19, in 1,728 MIP sequenced unaffected siblings form the Simons Simplex Collection, or in 192 HRM analyzed chromosomes from healthy Belgian controls.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Abecasis, G.R. et al. An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56–65 (2012). source

      Not checked in the free run.

  • The quote only partly states this claim.

    Findingown data

    TP53 expression was significantly increased in the patients.

    “Expression levels of TP53, reported upregulated in HT29 cells incubated with ADNP antioligodeoxynucleotide32, were significantly increased (Supplementary Fig. 3g)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Zamostiano, R. et al. Cloning and characterization of the human activity-dependent neuroprotective protein. J. Biol. Chem. 276, 708–714 (2001). source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The patients' dysmorphic features included a prominent forehead, high hairline, eversion or notch of the eyelid, broad nasal bridge, thin upper lip and smooth or long philtrum.

    “Dysmorphic features include a prominent forehead, high hairline, eversion or notch of the eyelid, broad nasal bridge, thin upper lip and smooth/long philtrum (Figure 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    All identified ADNP mutations were heterozygous frameshift or nonsense variants located in the C-terminal part of the last exon and introduced a premature termination codon.

    “All mutations are heterozygous frameshift or nonsense variants in the C-terminal part of the last exon of ADNP and result in a premature termination codon (Table 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The authors found no X-chromosomal, compound heterozygous or homozygous variants in known intellectual disability or autism spectrum disorder genes.

    “Neither did we find X-chromosomal, compound or homozygous variants in known intellectual disability/ASD genes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The authors identified ten patients with autism spectrum disorder and additional shared clinical features, including intellectual disability and facial dysmorphisms, who carry mutations in ADNP.

    “Here, we report 10 patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/SNF remodeling complex.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The patients frequently had hypotonia, feeding problems in infancy and congenital heart defects.

    “Other frequent findings include hypotonia, feeding problems in infancy and congenital heart defects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For nine of the ten patients, parental testing was available and the ADNP mutation appeared de novo in every case.

    “For nine patients the parents were available for testing and in each case the mutation appeared de novo (Table 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Dysmorphic features varied between patients, but a prominent forehead, broad nasal bridge, thin upper lip and smooth philtrum were frequently present.

    “Dysmorphic features vary from patient to patient, but a prominent forehead, broad nasal bridge, thin upper lip and smooth philtrum are frequently present.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    The mutations in patients 6 and 8 are identical and differ by only one amino acid from the mutation in patient 1.

    “The mutations in patients 6 and 8 are identical and differ only by a single amino acid from the mutation in patient 1.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The severity of the phenotype varied in the cohort, but all patients had some degree of autism spectrum disorder and all were intellectually disabled.

    “The severity of the phenotype in our cohort varies, but all patients exhibit various degrees of ASD and all are intellectually disabled.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    ADNP is a transcription factor that participates in the SWI/SNF chromatin remodeling complex.

    “a transcription factor involved in the SWI/SNF remodeling complex”
    • Also stated in: § Abstract · plain
      “The C-terminal part of ADNP directly interacts with ARID1A, SMARCA4 and SMARCC2, three essential components of the BAF complexes, the functional eukaryotic equivalent of the SWI/SNF complex in yeast that is involved in the regulation of gene expression36.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Mandel, S. & Gozes, I. Activity-dependent neuroprotective protein constitutes a novel element in the SWI/SNF chromatin remodeling complex. J. Biol. Chem. 282, 34448–34456 (2007). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    De novo loss-of-function mutations in ADNP had previously been reported in two autism spectrum disorder patients by whole-exome sequencing and targeted resequencing, but those studies did not establish locus-specific significance for causality.

    “De novo loss of function mutations in this gene had previously been identified in two patients by WES2 and targeted resequencing16 of patients with ASD. In those studies however, causal relationship did not reach locus-specific significance.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [2] O'Roak, B.J. et al. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 485, 246–250 (2012). source

      Not checked in the free run.

    • cites [16] O'Roak, B.J. et al. Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science 338, 1619–1622 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Because ADNP expression is controlled by an autoregulatory negative feedback loop, the overall upregulation might result from the mutant protein's inability to bind the ADNP promoter.

    “Since ADNP expression is under control of an autoregulatory negative feedback loop33, the overall upregulation might be a consequence of the inability of the mutant protein to bind the ADNP promoter.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] Aboonq, M.S., Vasiliou, S.A., Haddley, K., Quinn, J.P. & Bubb, V.J. Activity-dependent neuroprotective protein modulates its own gene expression. J. Mol. Neurosci. 46, 33–39 (2012). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The clustering of de novo rare variants suggests a mutation predisposition mechanism, possibly due to local genomic architecture.

    “Clustering of de novo, rare variants is suggestive of a mutation predisposition mechanism, potentially as a result of a particular local genomic architecure.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The discrepancy for the other mouse genes may be due to differences in tissue and developmental stage between knockout mice and human cell lines.

    “This may be the consequence of differences in tissue and developmental stage between the knockout mice and the human cell lines.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    An inherited p.Gly1094Profs*5 ADNP mutation identified by molecular inversion probe sequencing is located nine amino acids from the C-terminal end and is not associated with any protein domains.

    “An inherited p.Gly1094Profs*5 mutation was identified by MIP sequencing16 but the reported frameshift is the ninth amino acid from the C-terminal end of the protein and not associated with any protein domains.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] O'Roak, B.J. et al. Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science 338, 1619–1622 (2012). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The increase in TP53 may result from augmented cellular stress due to overall deregulation of genes under ADNP transcriptional control.

    “possibly as a result of augmented cellular stress due to an overall deregulation of genes under transcriptional control of ADNP.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    ADNP+/- mice show tauopathy, neuronal cell death and abnormalities in social behaviour and cognitive functioning.

    “while ADNP+/- mice show tauopathy, neuronal cell death and abnormalities in social behaviour and cognitive functioning18,34.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [18] Vulih-Shultzman, I. et al. Activity-dependent neuroprotective protein snippet NAP reduces tau hyperphosphorylation and enhances learning in a novel transgenic mouse model. J. Pharmacol. Exp. Ther. 323, 438–449 (2007). source

      Not checked in the free run.

    • cites [34] Pinhasov, A. et al. Activity-dependent neuroprotective protein: a novel gene essential for brain formation. Brain Res. Dev. Brain Res. 144, 83–90 (2003). source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The authors' findings expand the phenotypic spectrum of SWI/SNF-related disorders, several of which are caused by mutations in direct interaction partners of ADNP.

    “These findings expand the phenotypic spectrum of SWI/SNF-related disorders, several of which are caused by mutations in direct interaction partners of ADNP.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    Whole-exome sequencing variants were filtered to exclude low-quality variants, intronic or intergenic variants except splice sites, and variants inherited from parents.

    “Variants were filtered by VariantDB (see URLs, manuscript in preparation) to exclude variants with (1) low quality, using thresholds based on correlation between NGS data and SNP-chip genotyping; (2) intronic or intergenic location, except splice sites; and (3) inheritance from the parents.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Reference genes YWHAZ and HPRT were selected according to geNorm calculations.

    “YWHAZ and HPRT were selected as reference genes, according to geNorm calculations54.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Vandesompele, J. et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3, 34.1–34.11 (2002). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted). May combine two claims.

    Interpretationreasoning

    The authors hypothesize that the mutant ADNP protein with an altered C-terminal structure will hamper BAF complex recruitment while still occupying DNA binding sites.

    “Hence, it can be hypothesised that the mutant protein with an altered C-terminal structure will hamper the recruitment of the BAF complex, while it still occupies DNA binding sites.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    A switch in BAF complex composition is essential for initiating post-mitotic activity-dependent dendritic outgrowth and axonal development.

    “A switch of complex composition is essential for initiation of post-mitotic activity-dependent dendritic outgrowth and axonal development.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Lessard, J. et al. An essential switch in subunit composition of a chromatin remodeling complex during neural development. Neuron 55, 201–215 (2007). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The amplification efficiency of the qPCR primers was assessed and confirmed to be above 1.85.

    “The amplification efficiency of the different primers was assessed and confirmed to be above 1.85.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S1 (asserted). May combine two claims.

    Interpretationown data

    Because mutant RNA was detected in the patients, the authors hypothesize that the mutant ADNP protein competes with wildtype protein in aberrant interaction with the BAF complex.

    “As we were able to detect mutant RNA in our patients, we hypothesize that the mutant ADNP protein competes with the wildtype protein in aberrant interaction with the BAF complex.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Clinical evaluation was performed by at least one expert clinical geneticist.

    “Clinical evaluation was performed by at least one expert clinical geneticist.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Wildtype ADNP directly binds target genomic regions and mediates recruitment of the BAF complex through its C-terminal end.

    “Wildtype ADNP directly binds target genomic regions and mediates the recruitment of the BAF complex through the C-terminal end.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Inheritance determination and validation for molecular inversion probe-discovered patients were performed by Sanger sequencing.

    “Inheritance determination and validation were performed by Sanger sequencing.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Reported de novo mutations were confirmed by an independent technique such as Sanger sequencing.

    “Presence of reported (de novo) mutations were confirmed by an independent technique such as Sanger sequencing.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Expression values from two cDNA syntheses from two RNA isolations per patient were compared with values from eight control individuals.

    “Expression values of two cDNA syntheses originating from two different RNA isolations per patient were compared to the values obtained from eight control individuals.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    BAF complexes are ATP-dependent chromatin remodeling complexes consisting of 15 subunits, including one of the ATPase core subunits SMARCA4 or SMARCA2.

    “These ATP-dependent chromatin remodelling complexes consist of 15 subunits, including one of both ATPase core subunits SMARCA4 or SMARCA237.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Ronan, J.L., Wu, W. & Crabtree, G.R. From neural development to cognition: unexpected roles for chromatin. Nat. Rev. Genet. 14, 347–359 (2013). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Written informed consent was obtained for all patients, and consent for publication of photographs was obtained for patients 1, 2, 4, 5, 6 and 8.

    “Written informed consent for inclusion in the study was obtained for all patients and consent for the publication of photographs was obtained for patients 1, 2, 4, 5, 6 and 8.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The phenotype associated with mutations in these BAF component genes ranges from non-syndromic intellectual disability with hypotonia and speech delay to recognizable syndromes such as Coffin-Siris syndrome and Nicolaides-Baraitser syndrome.

    “The phenotype associated with mutations in these genes ranges from non-syndromic intellectual disability with hypotonia and speech delay to recognizable syndromes such as the Coffin-Siris syndrome and Nicolaides-Baraitser syndrome.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [39] Kosho, T. et al. Clinical correlations of mutations affecting six components of the SWI/SNF complex: detailed description of 21 patients and a review of the literature. Am. J. Med. Genet. 161A, 1221–1237 (2013). source

      Not checked in the free run.

    • cites [40] Santen, G.W. et al. Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients. Hum. Mutat. 34, 1519–1528 (2013). source

      Not checked in the free run.

    • cites [41] Hoyer, J. et al. Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability. Am. J. Hum. Genet. 90, 565–572 (2012). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Mutations in six BAF complex components (SMARCB1, SMARCA4, SMARCA2, SMARCE1, ARID1A and ARID1B) have been reported in patients with intellectual disability.

    “Interestingly, mutations in patients with intellectual disability have been reported in six components of these complexes (SMARCB1, SMARCA4, SMARCA2, SMARCE1, ARID1A and ARID1B).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [39] Kosho, T. et al. Clinical correlations of mutations affecting six components of the SWI/SNF complex: detailed description of 21 patients and a review of the literature. Am. J. Med. Genet. 161A, 1221–1237 (2013). source

      Not checked in the free run.

    • cites [40] Santen, G.W. et al. Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients. Hum. Mutat. 34, 1519–1528 (2013). source

      Not checked in the free run.

    • cites [41] Hoyer, J. et al. Haploinsufficiency of ARID1B, a member of the SWI/SNF-a chromatin-remodeling complex, is a frequent cause of intellectual disability. Am. J. Hum. Genet. 90, 565–572 (2012). source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    This impairment will lead to diminished BAF complex functionality and ultimately deregulation of several cellular processes.

    “This will lead to a diminished functionality of the complex and ultimately to deregulation of several cellular processes.”
    Quote in the paperSubstantial claim
37 of 37

  • The paper relies on this without support.

    The cohort of 5,776 patients screened is representative of the broader autism spectrum disorder population, so the observed ADNP mutation frequency can be used to estimate the proportion of autism spectrum disorder cases explained by ADNP.

    “We estimate this gene to be mutated in at least 0.17% of ASD cases”
    “Mutations in ADNP may explain the etiology of 0.17% of patients with ASD (95% binomial confidence interval: 0.083% - 0.32%)”

  • The paper relies on this without support.

    The control cohorts used for comparison are representative of the general population and comparable to the patient cohort for the ADNP truncating-mutation frequency analysis.

    “The frequency of truncating mutations in ADNP is significantly higher (p: 0.001852, odds ratio 13.24668, one-sided Fisher’s exact test) in patients compared to the ESP and Simons Siblings controls.”
2 of 2

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Authors
Helsmoortel, C., Vulto-van Silfhout, A. T., Coe, B. P., Vandeweyer, G., Rooms, L., van den Ende, J., Schuurs-Hoeijmakers, J. H. M., Marcelis, C. L., Willemsen, M. H., Vissers, L. E. L. M., Yntema, H. G., Bakshi, M., Wilson, M., Witherspoon, K. T., Malmgren, H., Nordgren, A., Annerén, G., Fichera, M., Bosco, P., Romano, C., de Vries, B. B. A., Kleefstra, T., Kooy, R. F., Eichler, E. E., & Van der Aa, N.
Affiliations
  • University of Antwerp (BE)
  • Howard Hughes Medical Institute (US)
  • Radboud University Medical Center (NL)
  • Westmead Hospital (AU)
  • Children's Hospital at Westmead (AU)
  • Karolinska Institutet (SE)
  • Uppsala University (SE)
  • University of Catania (IT)
  • Oasi Maria SS (IT)
  • Radboud University Nijmegen (NL)
Corresponding author
Kooy, R Frank
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2014-02-16
Volume
46
Issue
4
Pages
380-384
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng.2899
PMC
PMC3990853
OpenAlex
W2097496333
Semantic Scholar
64e7e00926d98492f0281d741ea5654bf44f343f
Cited by
354
References
58
Citations by year
2026: 19 · 2025: 31 · 2024: 43 · 2023: 24 · 2022: 28 · 2021: 25 · 2020: 32 · 2019: 30 · 2018: 28 · 2017: 30 · 2016: 28 · 2015: 21 · 2014: 13
FWCI
20.09
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
National Institute of Mental Health (R01MH101221)
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 › Genomics and Rare Diseases
Keywords
autism spectrum disorder, ADNP, de novo mutations, SWI/SNF complex, intellectual disability, facial dysmorphism, transcription factors, genetic diagnosis, genetic heterogeneity
MeSH terms
Abnormalities, Multiple, Base Sequence, Child Development Disorders, Pervasive, Chromosomal Proteins, Non-Histone, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Transcription Factors, Frameshift Mutation, Sequence Analysis, DNA, Codon, Nonsense, Homeodomain Proteins, Gene Components, Exome, Real-Time Polymerase Chain Reaction

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