Publication
Title
Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of Cornelia de Lange syndrome with predominant mental retardation
Author
Abstract
Mutations in the cohesin regulators NIPBL and ESCO2 are causative of the Cornelia de Lange syndrome (CdLS) and Roberts or SC phocomelia syndrome, respectively. Recently, mutations in the cohesin complex structural component SMC1A have been identified in two probands with features of CdLS. Here, we report the identification of a mutation in the gene encoding the complementary subunit of the cohesin heterodimer, SMC3, and 14 additional SMC1A mutations. All mutations are predicted to retain an open reading frame, and no truncating mutations were identified. Structural analysis of the mutant SMC3 and SMC1A proteins indicate that all are likely to produce functional cohesin complexes, but we posit that they may alter their chromosome binding dynamics. Our data indicate that SMC3 and SMC1A mutations ( 1) contribute to similar to 5% of cases of CdLS, ( 2) result in a consistently mild phenotype with absence of major structural anomalies typically associated with CdLS, and ( 3) in some instances, result in a phenotype that approaches that of apparently nonsyndromic mental retardation.
Language
English
Source (journal)
The American journal of human genetics / American Society of Human Genetics [Bethesda, Md] - New York, N.Y., 1949, currens
Publication
New York, N.Y. : 2007
ISSN
0002-9297 [print]
1537-6605 [online]
Volume/pages
80 :3 (2007) , p. 485-494
ISI
000244403300009
Full text (Publisher's DOI)
UAntwerpen
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 05.11.2018
Last edited 06.09.2021