ArticleGenome medicine2019
Re-analysis of whole-exome sequencing data uncovers novel diagnostic variants and improves molecular diagnostic yields for sudden death and idiopathic diseases.
Article in Genome medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Molecular autopsy in unexplained sudden death: a systematic review and meta-analysis of ACMG-corrected diagnostic yield, genomic architecture, and family translation.International journal of legal medicine · 2026Pooled it
- The clinical utility of exome and genome sequencing across clinical indications: a systematic review.Human genetics · 2021Pooled it
- Genomic Strategies in Pediatric Care: Addressing Rare Diseases in Children.Children (Basel, Switzerland) · 2026Review
- Molecular mechanisms of sudden unexplained death and recent updates on molecular autopsy strategies for forensic investigation.International journal of legal medicine · 2026Review
- Diagnostic utility of clinical genome reanalysis in rare pediatric disorders using long-read sequencing.HGG advances · 2026Article
- Diagnostic Yield After Postnatal Reanalysis of Prenatal Exome Sequencing Results.Prenatal diagnosis · 2026Article
- Allele age estimators designed for whole-genome datasets show only a moderate reduction in performance when applied to whole-exome datasets.G3 (Bethesda, Md.) · 2025Article
- Diagnostic Utility of Trio-Exome Sequencing for Children With Neurodevelopmental Disorders.JAMA network open · 2025Article
- Approaches to Evaluate Whole Exome Sequencing Data That Incorporate Genetic Intolerance Scores for Congenital Anomalies, Including Intronic Regions Adjacent to Exons.Molecular genetics & genomic medicine · 2025Article
- Genetic Background and Clinical Phenotype in an Italian Cohort with Inherited Arrhythmia Syndromes and Arrhythmogenic Cardiomyopathy (ACM): A Whole-Exome Sequencing Study.International journal of molecular sciences · 2025Article
- The Enigma of West Syndrome: A Case of Infantile Spasms Without Genetic Clues.Case reports in pediatrics · 2025Article
- Hypermagnesemia with Dystonia Type 2: Case Report of a New SLC30A10 Variant.Journal of pharmacy & bioallied sciences · 2024Article
- Article
- A Curious Case of Severe Recurrent Hypocalcemia.Cureus · 2024Article
- Article
- 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
- Semiautomated approach focused on new genomic information results in time and effort-efficient reannotation of negative exome data.Human genetics · 2024Article
- Bioinformatics of germline variant discovery for rare disease diagnostics: current approaches and remaining challenges.Briefings in bioinformatics · 2024Review
- Reanalysis of whole-exome sequencing (WES) data of children with neurodevelopmental disorders in a standard patient care context.European journal of pediatrics · 2024Article
- The application of whole-exome sequencing in the early diagnosis of rare genetic diseases in children: a study from Southeastern China.Frontiers in pediatrics · 2024Article
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10 authors.
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Abstract
backgroundWhole-exome sequencing (WES) has become an efficient diagnostic test for patients with likely monogenic conditions such as rare idiopathic diseases or sudden unexplained death. Yet, many cases remain undiagnosed. Here, we report the added diagnostic yield achieved for 101 WES cases re-analyzed 1 to 7 years after initial analysis.
methodsOf the 101 WES cases, 51 were rare idiopathic disease cases and 50 were postmortem "molecular autopsy" cases of early sudden unexplained death. Variants considered for reporting were prioritized and classified into three groups: (1) diagnostic variants, pathogenic and likely pathogenic variants in genes known to cause the phenotype of interest; (2) possibly diagnostic variants, possibly pathogenic variants in genes known to cause the phenotype of interest or pathogenic variants in genes possibly causing the phenotype of interest; and (3) variants of uncertain diagnostic significance, potentially deleterious variants in genes possibly causing the phenotype of interest.
resultsInitial analysis revealed diagnostic variants in 13 rare disease cases (25.4%) and 5 sudden death cases (10%). Re-analysis resulted in the identification of additional diagnostic variants in 3 rare disease cases (5.9%) and 1 sudden unexplained death case (2%), which increased our molecular diagnostic yield to 31.4% and 12%, respectively.
conclusionsThe basis of new findings ranged from improvement in variant classification tools, updated genetic databases, and updated clinical phenotypes. Our findings highlight the potential for re-analysis to reveal diagnostic variants in cases that remain undiagnosed after initial WES.
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