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Am J Hum Genet. 2011 Jul 15;89(1):176-82. doi: 10.1016/j.ajhg.2011.06.006.

Mutations in the alpha 1,2-mannosidase gene, MAN1B1, cause autosomal-recessive intellectual disability.

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  • 1Molecular Neuropsychiatry and Development Lab, Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.

Erratum in

  • Am J Hum Genet. 2011 Aug 12;89(2):348.

Abstract

We have used genome-wide genotyping to identify an overlapping homozygosity-by-descent locus on chromosome 9q34.3 (MRT15) in four consanguineous families affected by nonsyndromic autosomal-recessive intellectual disability (NS-ARID) and one in which the patients show additional clinical features. Four of the families are from Pakistan, and one is from Iran. Using a combination of next-generation sequencing and Sanger sequencing, we have identified mutations in the gene MAN1B1, encoding a mannosyl oligosaccharide, alpha 1,2-mannosidase. In one Pakistani family, MR43, a homozygous nonsense mutation (RefSeq number NM_016219.3: c.1418G>A [p.Trp473*]), segregated with intellectual disability and additional dysmorphic features. We also identified the missense mutation c. 1189G>A (p.Glu397Lys; RefSeq number NM_016219.3), which segregates with NS-ARID in three families who come from the same village and probably have shared inheritance. In the Iranian family, the missense mutation c.1000C>T (p.Arg334Cys; RefSeq number NM_016219.3) also segregates with NS-ARID. Both missense mutations are at amino acid residues that are conserved across the animal kingdom, and they either reduce k(cat) by ∼1300-fold or disrupt stable protein expression in mammalian cells. MAN1B1 is one of the few NS-ARID genes with an elevated mutation frequency in patients with NS-ARID from different populations.

Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

PMID:
21763484
[PubMed - indexed for MEDLINE]
PMCID:
PMC3135808
Free PMC Article
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