X chromosome exome sequencing reveals a novel ALG13 mutation in a nonsyndromic intellectual disability family with multiple affected male siblings.

Abstract

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.

• Authors: Nesrine Bissar-Tadmouri, Whithey L Donahue, Lihadh Al-Gazali, Stanley F Nelson, Pinar Bayrak-Toydemir, Sibel Kantarci
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 164A Issue 1 Pg. 164-9 (Jan 2014) ISSN: 1552-4833 [Electronic] United States
• PMID: 24501762 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Wiley Periodicals, Inc.

Chemical References

• ALG13 protein, human
• N-Acetylglucosaminyltransferases

Topics

• Chromosome Mapping
• Chromosomes, Human, X
• Exome
• Genes, X-Linked
• Genome-Wide Association Study
• Humans
• Intellectual Disability (genetics)
• Male
• Mutation
• Mutation, Missense
• N-Acetylglucosaminyltransferases (genetics)
• Pedigree
• Sequence Analysis, DNA
• Sex Factors
• Siblings