Proband‐Only Exome Sequencing for Intellectual Disability in Iran: Diagnostic Yield and Genetic Insights

ABSTRACT Intellectual disability (ID) is a leading cause for referral to genetic services, with the most severe cases typically attributed to single genetic defects. This study aimed to evaluate the diagnostic yield of cost‐effective proband‐only exome sequencing for individuals diagnosed with ID wi...

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Veröffentlicht in:American journal of medical genetics. Part A Jg. 197; H. 4; S. e63915 - n/a
Hauptverfasser: Ghalamkari, Safoura, Mianesaz, Hamidreza, Chitsaz, Ahmad, Ghazavi, Mohammadreza, Salehi, Mansoor
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Hoboken, USA John Wiley & Sons, Inc 01.04.2025
Wiley Subscription Services, Inc
Schlagworte:
Adolescent
Adult
Child
Child, Preschool
Consanguinity
Copy number
DNA Copy Number Variations - genetics
Exome - genetics
Exome Sequencing - methods
Female
Genetic Predisposition to Disease
Genetic Testing
Genetics
Humans
Intellectual disabilities
intellectual disability
Intellectual Disability - diagnosis
Intellectual Disability - epidemiology
Intellectual Disability - genetics
Intellectual Disability - pathology
Iran - epidemiology
Iranian population
Male
proband‐only exome sequencing
Whole genome sequencing
Iran
intellectual disability
Iranian population
proband‐only exome sequencing
ISSN:1552-4825, 1552-4833, 1552-4833
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Zusammenfassung:ABSTRACT Intellectual disability (ID) is a leading cause for referral to genetic services, with the most severe cases typically attributed to single genetic defects. This study aimed to evaluate the diagnostic yield of cost‐effective proband‐only exome sequencing for individuals diagnosed with ID within the Iranian population for the first time where a high rate of parental consanguinity exists. A total of 99 unrelated patients with ID were investigated by exome sequencing during 8 years. As a result, 43 pathogenic/likely pathogenic variants were identified in 40 patients, indicating a molecular diagnostic rate of 40.4% (40/99). The inclusion of five chromosomal copy number variations in the subsequent analysis increased the diagnostic rate of proband‐only exome sequencing to 45.4% (45/99). Additionally, parental testing revealed five de novo variants. This contributed to a total diagnostic rate of 50.5% (50/99). In our study, proband‐only exome sequencing achieved a remarkable diagnostic rate, identifying nearly half of the ID cases. This rate of diagnosis could be primarily attributed to prevalent consanguineous marriage in the Iranian population and the rare identification of de novo variants. With the ongoing advancements in neurogenetics, proband‐only exome sequencing demonstrates significant potential as a future cost‐effective diagnostic approach in Iran.
Bibliographie:Funding
This study received funding from the Medical University of Isfahan scholarship [grant number 396131], which supported the analysis, collection, and interpretation of data.
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ISSN:1552-4825
1552-4833
1552-4833
DOI:10.1002/ajmg.a.63915