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X chromosome exome sequencing reveals a novel ALG 13 mutation in a nonsyndromic intellectual disability family with multiple affected male siblings
Author(s) -
BissarTadmouri Nesrine,
Donahue Whithey L.,
AlGazali Lihadh,
Nelson Stanley F.,
BayrakToydemir Pinar,
Kantarci Sibel
Publication year - 2014
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36233
Subject(s) - missense mutation , exome sequencing , sanger sequencing , genetics , intellectual disability , exome , mutation , biology , gene
X‐linked intellectual disability (XLID) is a heterogeneous condition associated with mutations in >100 genes, accounting for over 10% of all cases of intellectual impairment. The majority of XLID cases show nonsyndromic forms (NSXLID), in which intellectual disability is the sole clinically consistent manifestation. Here we performed X chromosome exome (X‐exome) sequencing to identify the causative mutation in an NSXLID family with four affected male siblings and five unaffected female siblings. The X‐exome sequencing at 88× coverage in one affected male sibling revealed a novel missense mutation (p.Tyr1074Cys) in the asparagine‐linked glycosylation 13 homolog ( ALG13 ) gene. Segregation analysis by Sanger sequencing showed that the all affected siblings were hemizygous and the mother was heterozygous for the mutation. Recently, a de novo missense mutation in ALG13 has been reported in a patient with X‐linked congenital disorders of glycosylation type I. Our study reports the first case of NSXLID caused by a mutation in ALG13 involved in protein N ‐glycosylation. © 2013 Wiley Periodicals, Inc.