Novel collagen VI mutations identified in Chinese patients with Ullrich congenital muscular dystrophy

World J Pediatr. 2014 May;10(2):126-32. doi: 10.1007/s12519-014-0481-1. Epub 2014 May 7.

Abstract

Background: We determined the clinical and molecular genetic characteristics of 8 Chinese patients with Ullrich congenital muscular dystrophy (UCMD).

Methods: Clinical data of probands were collected and muscle biopsies of patients were analyzed. Exons of COL6A1, COL6A2 and COL6A3 were analyzed by direct sequencing. Mutations in COL6A1, COL6A2 and COL6A3 were identified in 8 patients.

Results: Among these mutations, 5 were novel [three in the triple helical domain (THD) and 2 in the second C-terminal (C2) domain]. We also identified five known missense or in-frame deletion mutations in THD and C domains. Immunohistochemical studies on muscle biopsies from patients showed reduced level of collagen VI at the muscle basement membrane and mis-localization of the protein in interstitial and perivascular regions.

Conclusions: The novel mutations we identified underscore the importance of THD and C2 domains in the assembly and function of collagen VI, thereby providing useful information for the genetic counseling of UCMD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Amino Acid Substitution
  • Biopsy
  • Child
  • Child, Preschool
  • China
  • Codon
  • Collagen Type VI / genetics*
  • Female
  • Frameshift Mutation
  • Humans
  • Immunohistochemistry
  • Male
  • Muscular Dystrophies / diagnosis
  • Muscular Dystrophies / genetics*
  • Mutation*
  • Mutation, Missense
  • Polymorphism, Single Nucleotide
  • Sclerosis / diagnosis
  • Sclerosis / genetics*
  • Sequence Deletion

Substances

  • COL6A2 protein, human
  • Codon
  • Col6a1 protein, human
  • Collagen Type VI

Supplementary concepts

  • Scleroatonic muscular dystrophy