Diagnostic power and clinical impact of exome sequencing in a cohort of 500 patients with rare diseases.
diagnostic yield
exome sequencing
incidental findings
rare diseases
secondary findings
Journal
American journal of medical genetics. Part C, Seminars in medical genetics
ISSN: 1552-4876
Titre abrégé: Am J Med Genet C Semin Med Genet
Pays: United States
ID NLM: 101235745
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
09
10
2020
revised:
03
11
2020
accepted:
09
11
2020
pubmed:
2
12
2020
medline:
18
9
2021
entrez:
1
12
2020
Statut:
ppublish
Résumé
Rare diseases comprise a diverse group of conditions, most of which involve genetic causes. We describe the variable spectrum of findings and clinical impacts of exome sequencing (ES) in a cohort of 500 patients with rare diseases. In total, 164 primary findings were reported in 158 patients, representing an overall diagnostic yield of 31.6%. Most of the findings (61.6%) corresponded to autosomal dominant conditions, followed by autosomal recessive (25.6%) and X-linked (12.8%) conditions. These patients harbored 195 variants, among which 43.6% are novel in the literature. The rate of molecular diagnosis was considerably higher for prenatal samples (67%; 4/6), younger children (44%; 24/55), consanguinity (50%; 3/6), gastrointestinal/liver disease (44%; 16/36) and syndromic/malformative conditions (41%; 72/175). For 15.6% of the cohort patients, we observed a direct potential for the redirection of care with targeted therapy, tumor screening, medication adjustment and monitoring for disease-specific complications. Secondary findings were reported in 37 patients (7.4%). Based on cost-effectiveness studies in the literature, we speculate that the reports of secondary findings may influence an increase of 123.2 years in the life expectancy for our cohort, or 0.246 years/cohort patient. ES is a powerful method to identify the molecular bases of monogenic disorders and redirect clinical care.
Identifiants
pubmed: 33258288
doi: 10.1002/ajmg.c.31860
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
955-964Informations de copyright
© 2020 Wiley Periodicals LLC.
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