Molecular genetics of the POMT1-related muscular dystrophy-dystroglycanopathies

Mutat Res Rev Mutat Res. 2018 Oct-Dec:778:45-50. doi: 10.1016/j.mrrev.2018.09.002. Epub 2018 Sep 12.

Abstract

Protein O-mannosyltransferase 1 (POMT1) is a critical enzyme participating in the first step of protein O-mannosylation. Mutations in the coding gene, POMT1, have been described to be related to a series of autosomal recessive disorders associated with defective alpha-dystroglycan glycosylation, later termed muscular dystrophy-dystroglycanopathies (MDDGs). MDDGs are characterized by a broad phenotypic spectrum of congenital muscular dystrophy or later-onset limb-girdle muscular dystrophy, accompanied by variable degrees of intellectual disability, brain defects, and ocular abnormalities. To date, at least 76 disease-associated mutations in the POMT1 gene, including missense, nonsense, splicing, deletion, insertion/duplication, and insertion-deletion mutations, have been reported in the literature. In this review, we highlight the present knowledge of the identified disease-associated POMT1 gene mutations and genetic animal models related to the POMT1 gene. This review may help further normative classification of phenotypes, assist in definite clinical and genetic diagnoses, and genetic counseling, and may comprehensively improve our understanding of the basis of complex phenotypes and possible pathogenic mechanisms involved.

Keywords: Genetics; Muscular dystrophy-dystroglycanopathy; Mutation; The POMT1 gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing / genetics
  • Codon, Nonsense / genetics
  • Humans
  • INDEL Mutation / genetics
  • Mannosyltransferases / genetics*
  • Muscular Dystrophies / diagnosis
  • Muscular Dystrophies / genetics*
  • Muscular Dystrophies / pathology
  • Mutation, Missense / genetics
  • Walker-Warburg Syndrome / diagnosis
  • Walker-Warburg Syndrome / genetics*
  • Walker-Warburg Syndrome / pathology

Substances

  • Codon, Nonsense
  • Mannosyltransferases
  • protein O-mannosyltransferase