Publication
Title
Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort
Author
Abstract
AdamsOliver syndrome (AOS) is a rare developmental disorder, characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Autosomal dominant forms of AOS are linked to mutations in ARHGAP31, DLL4, NOTCH1 or RBPJ, while DOCK6 and EOGT underlie autosomal recessive inheritance. Data on the frequency and distribution of mutations in large cohorts are currently limited. The purpose of this study was therefore to comprehensively examine the genetic architecture of AOS in an extensive cohort. Molecular diagnostic screening of 194 AOS/ACC/TTLD probands/families was conducted using next‐generation and/or capillary sequencing analyses. In total, we identified 63 (likely) pathogenic mutations, comprising 56 distinct and 22 novel mutations, providing a molecular diagnosis in 30% of patients. Taken together with previous reports, these findings bring the total number of reported disease variants to 63, with a diagnostic yield of 36% in familial cases. NOTCH1 is the major contributor, underlying 10% of AOS/ACC/TTLD cases, with DLL4 (6%), DOCK6 (6%), ARHGAP31 (3%), EOGT (3%), and RBPJ (2%) representing additional causality in this cohort. We confirm the relevance of genetic screening across the AOS/ACC/TTLD spectrum, highlighting preliminary but important genotypephenotype correlations. This cohort offers potential for further gene identification to address missing heritability.
Language
English
Source (journal)
Human mutation. - New York, N.Y.
Human mutation. - New York, N.Y.
Publication
New York, N.Y. : 2018
ISSN
1059-7794
Volume/pages
39 :9 (2018) , p. 1246-1261
ISI
000443229000009
Pubmed ID
29924900
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Bicuspid Related Aortopathy, a Vibrant Exploration (BRAVE).
Confidential
Deciphering hidden inheritance patterns using frequent itemset mining techniques on high throughput genomic data.
Clinical and (patho)genetic study of bicuspid aortic valve and associated aortic aneurysm.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 26.09.2018
Last edited 29.11.2021
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