ArticleEuropean journal of human genetics : EJHG2019
Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing.
Article in European journal of human genetics : EJHG, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
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- Contribution of families using the GenIDA database to the description of MED13L syndrome and literature review.Journal of neurodevelopmental disorders · 2025Review
- Reanalysis of unsolved prenatal exome sequencing for structural defects: diagnostic yield and contribution of postnatal/postmortem features.European journal of human genetics : EJHG · 2025Article
- Structural and functional insights into α-actinin isoforms and their implications in cardiovascular disease.The Journal of general physiology · 2025Review
- Use of Prenatal Exome Sequencing: Opinion Statement of the French Federation of Human Genetics Working Group.Prenatal diagnosis · 2025Review
- De NovoInternational journal of molecular sciences · 2025Review
- GPATCH11 variants cause mis-splicing and early-onset retinal dystrophy with neurological impairment.Nature communications · 2024Article
- Exome and genome sequencing in a heterogeneous population of patients with rare disease: Identifying predictors of a diagnosis.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Systematic reanalysis of genomic data by diagnostic laboratories: a scoping review of ethical, economic, legal and (psycho)social implications.European journal of human genetics : EJHG · 2024Article
- Novel compound heterozygous ABCA2 variants cause IDPOGSA, a variable phenotypic syndrome with intellectual disability.Journal of human genetics · 2024Article
- Auriculocondylar syndrome 2 caused by a novel PLCB4 variant in a male Chinese neonate: A case report and review of the literature.Molecular genetics & genomic medicine · 2024Review
- PACS gene family-related neurological diseases: limited genotypes and diverse phenotypes.World journal of pediatrics : WJP · 2024Article
- Expanding the Phenotype of Hereditary Congenital Facial Paresis Type 3.International journal of molecular sciences · 2023Article
- Relevance of next generation sequencing (NGS) data re-analysis in the diagnosis of monogenic diseases leading to organ failure.BMC medical genomics · 2023Article
- ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization.Genome medicine · 2023Article
- A second look at exome sequencing data: detecting mobile elements insertion in a rare disease cohort.European journal of human genetics : EJHG · 2023Article
- Clinical utility of periodic reinterpretation of CNVs of uncertain significance: an 8-year retrospective study.Genome medicine · 2023Article
- Combining globally search for a regular expression and print matching lines with bibliographic monitoring of genomic database improves diagnosis.Frontiers in genetics · 2023Article
- Exome sequencing allows detection of relevant pharmacogenetic variants in epileptic patients.The pharmacogenomics journal · 2022Article
- The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
21 authors at 20 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In clinical exome sequencing (cES), the American College of Medical Genetics and Genomics recommends limiting variant interpretation to established human-disease genes. The diagnostic yield of cES in intellectual disability and/or multiple congenital anomalies (ID/MCA) is currently about 30%. Though the results may seem acceptable for rare diseases, they mean that 70% of affected individuals remain genetically undiagnosed. Further analysis extended to all mutated genes in a research environment is a valuable strategy for improving diagnostic yields. This study presents the results of systematic research reanalysis of negative cES in a cohort of 313 individuals with ID/MCA. We identified 17 new genes not related to human disease, implicated 22 non-OMIM disease-causing genes recently or previously rarely related to disease, and described 1 new phenotype associated with a known gene. Twenty-six candidate genes were identified and are waiting for future recurrence. Overall, we diagnose 15% of the individuals with initial negative cES, increasing the diagnostic yield from 30% to more than 40% (or 46% if strong candidate genes are considered). This study demonstrates the power of such extended research reanalysis to increase scientific knowledge of rare diseases. These novel findings can then be applied in the field of diagnostics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.