Genetics of intellectual disability in consanguineous families.

Molecular Psychiatry
Hao HuHossein Najmabadi

Abstract

Autosomal recessive (AR) gene defects are the leading genetic cause of intellectual disability (ID) in countries with frequent parental consanguinity, which account for about 1/7th of the world population. Yet, compared to autosomal dominant de novo mutations, which are the predominant cause of ID in Western countries, the identification of AR-ID genes has lagged behind. Here, we report on whole exome and whole genome sequencing in 404 consanguineous predominantly Iranian families with two or more affected offspring. In 219 of these, we found likely causative variants, involving 77 known and 77 novel AR-ID (candidate) genes, 21 X-linked genes, as well as 9 genes previously implicated in diseases other than ID. This study, the largest of its kind published to date, illustrates that high-throughput DNA sequencing in consanguineous families is a superior strategy for elucidating the thousands of hitherto unknown gene defects underlying AR-ID, and it sheds light on their prevalence.

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Citations

Oct 14, 2018·Clinical Genetics·Kimia KahriziHans-Hilger Ropers
Feb 19, 2020·American Journal of Medical Genetics. Part a·Mohammed AlmannaiFowzan S Alkuraya
Aug 4, 2020·American Journal of Medical Genetics. Part a·Marianna FarnèPaolo Prontera
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Aug 9, 2020·Journal of Human Genetics·Ahmet Okay CaglayanMurat Gunel
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Methods Mentioned

BETA
exome sequencing

Software Mentioned

SIFT
CADD
PolyPhen2
Medical Resequencing Analysis Pipeline ( MERAP )
Medical Resequencing Analysis Pipeline
MERAP
Complete Genomics
MutationTaster
DRAGEN
CGA

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