Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Targeted next-generation sequencing analysis of 1,000 individuals with intellectual disability

Grozeva, Detelina, Carss, Keren, Spasic-Boskovic, Olivera, Tejada, Maria-Isabel, Gecz, Jozef, Shaw, Marie, Corbett, Mark, Haan, Eric, Thompson, Elizabeth, Friend, Kathryn, Hussain, Zaamin, Hackett, Anna, Field, Michael, Renieri, Alessandra, Stevenson, Roger, Schwartz, Charles, Floyd, James A.B., Bentham, Jamie, Cosgrove, Catherine, Keavney, Bernard, Bhattacharya, Shoumo, Hurles, Matthew and Raymond, F. Lucy 2015. Targeted next-generation sequencing analysis of 1,000 individuals with intellectual disability. Human Mutation 36 (12) , pp. 1197-1204. 10.1002/humu.22901

Full text not available from this repository.

Abstract

To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID‐associated genes using targeted next‐generation sequencing. Likely pathogenic rare variants were found in ∼11% of the cases (113 variants in 107/986 individuals: ∼8% of the individuals had a likely pathogenic loss‐of‐function [LoF] variant, whereas ∼3% had a known pathogenic missense variant). Variants in SETD5, ATRX, CUL4B, MECP2, and ARID1B were the most common causes of ID. This study assessed the value of sequencing a cohort of probands to provide a molecular diagnosis of ID, without the availability of DNA from both parents for de novo sequence analysis. This modeling is clinically relevant as 28% of all UK families with dependent children are single parent households. In conclusion, to diagnose patients with ID in the absence of parental DNA, we recommend investigation of all LoF variants in known genes that cause ID and assessment of a limited list of proven pathogenic missense variants in these genes. This will provide 11% additional diagnostic yield beyond the 10%–15% yield from array CGH alone.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Centre for Trials Research (CNTRR)
Publisher: Wiley
ISSN: 1059-7794
Date of Acceptance: 21 August 2015
Last Modified: 07 Apr 2021 16:00
URI: https://orca.cardiff.ac.uk/id/eprint/140284

Citation Data

Cited 110 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item