ArticleGenetics in medicine : official journal of the American College of Medical Genetics2015
Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 214 papers, 2 of them syntheses that pooled it.
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Who cites it
214 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Whole genome sequencing diagnostic yield for paediatric patients with suspected genetic disorders: systematic review, meta-analysis, and GRADE assessment.Archives of public health = Archives belges de sante publique · 2023Pooled it
- Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Pooled it
- A novel SLC9A1 mutation causes cerebellar ataxia.Journal of human genetics · 2018Trial
- Growth outcomes following recombinant human growth hormone therapy in Zhu-Tokita-Takenouchi-Kim syndrome.JCEM case reports · 2026Article
- Population-specific rare variants influence age at diagnosis in Korean inflammatory bowel disease.The Korean journal of internal medicine · 2026Article
- Nuclear speckles: a fundamental layer of gene regulation.Trends in cell biology · 2026Review
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- Accurate and cost-effective workflow integrating trio pooled-WES for novel gene discovery in neurodevelopmental disorders.European journal of human genetics : EJHG · 2026Article
- Phenotypic prediction of missense variants via deep contrastive learning.Nature biomedical engineering · 2026Article
- Genetics of selenoproteins and selenoprotein metabolism - An overview of current concepts and emerging aspects.Redox biology · 2026Review
- Interstitial cystitis: a phenotype and rare variant exome sequencing study.EBioMedicine · 2026Article
- ZTTK Syndrome Expanding the Cardiac Phenotype: A Case of Shone's Complex With a NovelCase reports in genetics · 2026Article
- Loss of ANK3 Function Causes a Recessive Neurodevelopmental Disorder with Cerebellar Ataxia.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Article
- A novel ASXL3 gene variant in a Chinese Boy causing Bainbridge.BMC infectious diseases · 2025Article
- GRIN2B-related neurodevelopmental disorders: genotype-phenotype correlations and therapeutic implications.Orphanet journal of rare diseases · 2025Article
- NGS Approaches in Clinical Diagnostics: From Workflow to Disease-Specific Applications.International journal of molecular sciences · 2025Review
- Biallelic MED29 variants cause pontocerebellar hypoplasia with cataracts.European journal of human genetics : EJHG · 2025Article
- Precision Medicine in Hematologic Malignancies: Evolving Concepts and Clinical Applications.Biomedicines · 2025Review
- Hypopituitarism: genetic, developmental, and acquired etiologies with a focus on the emerging concept of autoimmune hypophysitis.Endocrine journal · 2025Review
154 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors.
Funding
Abstract
purposeDespite the recognized clinical value of exome-based diagnostics, methods for comprehensive genomic interpretation remain immature. Diagnoses are based on known or presumed pathogenic variants in genes already associated with a similar phenotype. Here, we extend this paradigm by evaluating novel bioinformatics approaches to aid identification of new gene-disease associations.
methodsWe analyzed 119 trios to identify both diagnostic genotypes in known genes and candidate genotypes in novel genes. We considered qualifying genotypes based on their population frequency and in silico predicted effects we also characterized the patterns of genotypes enriched among this collection of patients.
resultsWe obtained a genetic diagnosis for 29 (24%) of our patients. We showed that patients carried an excess of damaging de novo mutations in intolerant genes, particularly those shown to be essential in mice (P = 3.4 × 10(-8)). This enrichment is only partially explained by mutations found in known disease-causing genes.
conclusionThis work indicates that the application of appropriate bioinformatics analyses to clinical sequence data can also help implicate novel disease genes and suggest expanded phenotypes for known disease genes. These analyses further suggest that some cases resolved by whole-exome sequencing will have direct therapeutic implications.
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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.