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

Am J Med Genet A. 2014 Jan;164A(1):164-9. doi: 10.1002/ajmg.a.36233.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • ALG13 protein, human
  • N-Acetylglucosaminyltransferases