Title
Challenges and opportunities in the investigation of unexplained intellectual disability using family-based whole-exome sequencingChallenges and opportunities in the investigation of unexplained intellectual disability using family-based whole-exome sequencing
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
Medical Genetics (MEDGEN)
Cognitive Genetics (COGNET)
Publication type
article
Publication
Copenhagen,
Subject
Human medicine
Source (journal)
Clinical genetics. - Copenhagen
Volume/pages
88(2015):2, p. 140-148
ISSN
0009-9163
ISI
000357692000008
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Intellectual disability (ID), characterized by an intellectual performance of at least 2 SD (standard deviations) below average is a frequent, lifelong disorder with a prevalence of 2-3%. Today, only for at most half of patients a diagnosis is made. Knowing the cause of the ID is important for patients and their relatives, as it allows for appropriate medical care, prognosis on further development of the disorder, familial counselling or access to support groups. Whole-exome sequencing (WES) now offers the possibility to identify the genetic cause for patients for which all previously available genetic tests, including karyotyping, specific gene analysis, or microarray analysis did not reveal causative abnormalities. However, data analysis of WES experiments is challenging. Here we present an analysis workflow implementable in any laboratory, requiring no bioinformatics knowledge. We demonstrated its feasibility on a cohort of 10 patients, in which we found a conclusive diagnosis in 3 and a likely diagnosis in 2 more patients. Of the three conclusive diagnoses, one was a clinically suspected mutation missed by Sanger sequencing, and one was an atypical presentation of a known monogenic disorder, highlighting two essential strengths of WES-based diagnostics.
E-info
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000357692000008&DestLinkType=RelatedRecords&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000357692000008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
https://repository.uantwerpen.be/docman/iruaauth/ab5caa/f24127093.pdf
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000357692000008&DestLinkType=CitingArticles&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
Handle