ReviewGenetics in medicine : official journal of the American College of Medical Genetics2019
A retrospective review of multiple findings in diagnostic exome sequencing: half are distinct and half are overlapping diagnoses.
Review in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed.
- Genome sequencing for the diagnosis of intellectual disability as a paradigm for rare diseases in the French healthcare setting: the prospective DEFIDIAG study.Genome medicine · 2025Trial
- Clinical and genetic spectrum of dual rare genetic diseases revealed by whole-exome sequencing in 14 pediatric patients.Orphanet journal of rare diseases · 2026Article
- Cross-species functional analysis of aResearch square · 2026Article
- Exome sequencing early in outpatient evaluation in NCGENES 2: Changing the course of the diagnostic odyssey?HGG advances · 2026Article
- The NeuroWES project: lessons learned from comprehensive phenotyping and genetic analysis of neurodevelopmental disorders over a decade.Human genetics · 2026Article
- First reported case of Turner syndrome with Krabbe disease in a child: a case report.Translational pediatrics · 2026Article
- Dual Renal and Cardiac Phenotypes Associated with Rare Variants Inherited from Both Parents.Internal medicine (Tokyo, Japan) · 2026Article
- Uncovering dual molecular diagnoses in families with complex phenotypes through structural and clinical studies of novel COL4A6 variants.QJM : monthly journal of the Association of Physicians · 2026Observational
- Article
- Dual molecular diagnosis of CEP290 and GLI3 mutations identified in an infant with leber congenital amaurosis and postaxial polydactyly, a Bardet-Biedl syndrome phenocopy.BMC ophthalmology · 2026Article
- Investigating concomitant RAG-2 and LRBA mutations in SCID and autoimmunity.Clinical and experimental immunology · 2026Article
- Single vs dual genetic disease in children with congenital anomalies and solid tumors.Genetics in medicine open · 2026Article
- Co-occurring DMD, GJA1, and novel FYCO1 variants in a proband from a consanguineous oculodentodigital dysplasia family: a rare multi-locus case report.Frontiers in genetics · 2026Article
- Infantile 22q11.2 deletion syndrome with secondary monogenic variants following inconclusive whole exome sequencing: a case report.Frontiers in pediatrics · 2026Article
- Investigating the interplay between prematurity and genetic variation in the context of rare developmental disorders.Genome medicine · 2025Article
- Nephrogenomics, precision medicine and the role of genetic testing in adult kidney disease management.Nature reviews. Nephrology · 2025Review
- Co-Occurrence of Variants in 3 Genes in a Patient with Congenital Skeletal Dysplasia and Cardiac Anomalies: Diagnostic Challenge Posed by a Blended Phenotype.Molecular syndromology · 2025Article
- Characterizing trends in clinical genetic testing: A single-center analysis of EHR data from 1.8 million patients over two decades.American journal of human genetics · 2025Article
- Coexistence of Rare Genetic Disorders in a Consanguineous Family: Case Study of KLHL24-Related Hypertrophic Cardiomyopathy and Char Syndrome.Molecular syndromology · 2025Article
- Navigating an Uninformative Genomic Test Result: A Practical Guide.Journal of paediatrics and child health · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
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Abstract
purposeWe evaluated clinical and genetic features enriched in patients with multiple Mendelian conditions to determine which patients are more likely to have multiple potentially relevant genetic findings (MPRF).
methodsResults of the first 7698 patients who underwent exome sequencing at Ambry Genetics were reviewed. Clinical and genetic features were examined and degree of phenotypic overlap between the genetic diagnoses was evaluated.
resultsAmong patients referred for exome sequencing, 2% had MPRF. MPRF were more common in patients from consanguineous families and patients with greater clinical complexity. The difference in average number of organ systems affected is small: 4.3 (multiple findings) vs. 3.9 (single finding) and may not be distinguished in clinic.
conclusionPatients with multiple genetic diagnoses had a slightly higher number of organ systems affected than patients with single genetic diagnoses, largely because the comorbid conditions affected overlapping organ systems. Exome testing may be beneficial for all cases with multiple organ systems affected. The identification of multiple relevant genetic findings in 2% of exome patients highlights the utility of a comprehensive molecular workup and updated interpretation of existing genomic data; a single definitive molecular diagnosis from analysis of a limited number of genes may not be the end of a diagnostic odyssey.
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