The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Second-tier trio exome sequencing after negative solo clinical exome sequencing: an efficient strategy to increase diagnostic yield and decipher molecular bases in undiagnosed developmental disorders
Open accessAbstract
Developmental disorders (DD), characterized by malformations/dysmorphism and/or intellectual disability, affecting around 3% of worldwide population, are mostly linked to genetic anomalies. Despite clinical exome sequencing (cES) centered on genes involved in human genetic disorders, the majority of patients affected by DD remain undiagnosed after solo-cES. Trio-based strategy is expected to facilitate variant selection thanks to rapid parental segregation. We performed a second step trio-ES (not only focusing on genes involved in human disorders) analysis in 70 patients with negative results after solo-cES. All candidate variants were shared with a MatchMaking exchange system to identify additional patients carrying variants in the same genes and with similar phenotype. In 18/70 patients (26%), we confirmed causal implication of nine OMIM-morbid genes and identified nine new strong candidate genes (eight de novo and one compound heterozygous variants). These nine new candidate genes were validated through the identification of patients with similar phenotype and genotype thanks to data sharing. Moreover, 11 genes harbored variants of unknown significance in 10/70 patients (14%). In DD, a second step trio-based ES analysis appears an efficient strategy in diagnostic and translational research to identify highly candidate genes and improve diagnostic yield.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Two missense WASF2 variants, c.113G > A (p.Arg38Gln) and c.494T > C (p.Leu165Pro), were identified in patients with autism and neurodevelopmental disorders.
“Two missense WASF2 variants, c.113G > A (p.Arg38Gln) and c.494T > C (p.Leu165Pro), were identified in patients with autism and NDDs103–105, but the functional alterations associated with brain disorders remain to be studied (Table 2g).”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [105]
The available indexed passages contain a reference-list entry for Tran Mau-Them et al. (2020), rather than findings from that paper; no section or page is provided. Searches for WASF2, both variant identifiers, and the protein changes found no passage addressing whether these variants were identified in patients with autism or neurodevelopmental disorders. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., et al. (2015) · Genetics in Medicine · doi:10.1038/gim.2015.30 · Cited by 32,594
Prevalence and architecture of de novo mutations in developmental disorders
Study, D. D. D. (2017) · Nature · doi:10.1038/nature21062 · Cited by 1,480
Lessons learned from additional research analyses of unsolved clinical exome cases
Eldomery, M. K., Coban-Akdemir, Z., Harel, T., Rosenfeld, J. A., Gambin, T., Stray-Pedersen, A., Küry, S., Mercier, S., Lessel, D., Denecke, J., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0412-6 · Cited by 230
Flagged first, then by citations
Research works printed but not linked: 20
- Carapito R, Ivanova EL, Morlon A et al (2019) ZMIZ1 variants cause a syndromic neurodevelopmental disorder. Am J Hum Genet 104(2):319–330 · DOI
- Duijkers FA, McDonald A, Janssens GE et al (2019) HNRNPR variants that Impair homeobox gene expression drive developmental disorders in humans. Am J Hum Genet 104(6):1040–1059 · DOI
- Esteve C, Francescatto L, Tan PL et al (2018) Loss-of-function mutations in UNC45A cause a syndrome associating cholestasis, diarrhea, impaired hearing, and bone fragility. Am J Hum Genet 102(3):364–374 · DOI
- Gerth-Kahlert C, Williamson K, Ansari M et al (2013) Clinical and mutation analysis of 51 probands with anophthalmia and/or severe microphthalmia from a single center. Mol Genet Genom Med 1(1):15–31 · DOI
- Gilissen C, Hoischen A, Brunner HG, Veltman JA (2012) Disease gene identification strategies for exome sequencing. Eur J Hum Genet 20(5):490–497 · DOI
- Gregor A, Sadleir LG, Asadollahi R et al (2018) De Novo variants in the F-box protein FBXO11 in 20 individuals with a variable neurodevelopmental disorder. Am J Hum Genet 103(2):305–316 · DOI
- Hennekan RC, Biesecker LG (2012) Next-generation sequencing demands next-generation phenotyping. Hum Mut 33(5):884–886 · DOI
- Jansen S, Geuer S, Pfundt R et al (2017) De Novo truncating mutations in the last and penultimate exons of PPM1D cause an intellectual disability syndrome. Am J Hum Genet 100(4):650–658 · DOI
- Kariminejad A, Dahl-Halvarsson M, Ravenscroft G et al (2017) TOR1A variants cause a severe arthrogryposis with developmental delay, strabismus and tremor. Brain 140(11):2851–2859 · DOI
- Liang L, Li X, Moutton S et al (2019) De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurological phenotypes. Hum Mol Genet 28(17):2937–2951 · DOI · Paper page
- Nambot S, Thevenon J, Kuentz P et al (2017) Clinical whole-exome sequencing for the diagnosis of rare disorders with congenital anomalies and/or intellectual disability: substantial interest of prospective annual reanalysis. Genet Med 20(6):645–654 · DOI
- Posey JE, Harel T, Liu P et al (2017) Resolution of disease phenotypes resulting from multilocus genomic variation. N Engl J Med 376(1):21–31 · DOI
- Sawyer SL, Hartley T, Dyment DA et al (2016) Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin Genet 89(3):275–284 · DOI
- Slavotinek A, Risolino M, Losa M et al (2017) De novo, deleterious sequence variants that alter the transcriptional activity of the homeoprotein PBX1 are associated with intellectual disability and pleiotropic developmental defects. Hum Mol Genet 26(24):4849–4860 · DOI
- Sobreira N, Schiettecatte F, Valle D, Hamosh A (2015) GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Hum Mutat 36(10):928–930 · DOI · Paper page
- Srivastava S, Gubbels CS, Dies K, Fulton A, Yu T, Sahin M (2017) Increased survival and partly preserved cognition in a patient with ACO2-related disease secondary to a novel variant. J Child Neurol 32(9):840–845 · DOI
- Tan TY, Lunke S, Chon B et al (2019) A head-to-head evaluation of the diagnostic efficacy and costs of trio versus singleton exome sequencing analysis. Eur J Hum Genet 27(12):1791–1799 · DOI
- Tokita MJ, Chen CA, Chitayat D et al (2018) De Novo missense variants in TRAF7 cause developmental delay, congenital anomalies, and dysmorphic features. Am J Hum Genet 103(1):154–162 · DOI
- Tran Mau-Them F, Guibaud L, Duplomb L et al (2019) De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy. Genet Med 21(4):1008–1014 · DOI
- Wright CF, FitzPatrick DR, Firth HV (2018) Paediatric genomics: diagnosing rare disease in children. Nat Rev Genet 19(5):253–268 · DOI
Cited by
Sorted by citations
The WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8
Metadata
- Authors
- Tran Mau-Them, F., Moutton, S., Racine, C., Vitobello, A., Bruel, A.-L., Nambot, S., Kushner, S. A., de Vrij, F. M. S., Lehalle, D., Jean-Marçais, N., Lecoquierre, F., Delanne, J., Thevenon, J., Poe, C., Jouan, T., Chevarin, M., Geneviève, D., Willems, M., Coubes, C., Houcinat, N., Masurel-Paulet, A., Mosca-Boidron, A.-L., Tisserant, E., Callier, P., Sorlin, A., Duffourd, Y., Faivre, L., Philippe, C., & Thauvin-Robinet, C.
- Affiliations
- CHU Dijon Bourgogne (FR)
- Inserm (FR)
- Erasmus MC (NL)
- ORCID
- Venue
- Human Genetics
- Published
- 2020-05-12
- Volume
- 139
- Issue
- 11
- Pages
- 1381-1390
- ISSN
- 0018-7348 (ISSN-L)
- 0340-6717
- 1432-1203
- OpenAlex
- W3024165433
- Cited by
- 14
- References
- 3
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 2
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- Locations
- Human Genetics (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- HAL (submittedVersion)
- Medical genetics (Research Centre of Medical Genetics of the Russian Academy of Medical Sciences) (submittedVersion, cc-by)
- Funders
- Plan d’Actions Régional pour l’Innovation - PARI
- Fonds Européen de DEveloppement Regional - FEDER
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- developmental disorders, trio exome sequencing, undiagnosed patients, diagnostic yield, de novo mutations, compound heterozygosity, variants of uncertain significance, candidate genes, intellectual disability, dysmorphic features
- MeSH terms
- Exome Sequencing, Developmental Disabilities, Female, Humans, Male, Intellectual Disability, Phenotype, Genetic Predisposition to Disease, Genomics, Exome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
