Candidate-gene testing for orphan limb-girdle muscular dystrophies

Acta Myol. 2008 Dec;27(3):90-7.

Abstract

The term limb-girdle muscular dystrophies (LGMD) identify about two dozens of distinct genetic disorders. Additional genes must play a role, since there are LGMD families excluded from any known locus. The aim of our work is to test a number of candidate genes in unclassified LGMD patient and control DNA samples. We selected the following 11 candidate genes: myozenin 1, 2 and 3, gamma-filamin, kinectin-1, enolase-3 beta, ZASP, TRIM 11 and TRIM 17, OZZ and zeta-sarcoglycan. These candidates were chosen for a combination of different reasons: chromosomal position, sequence homology, interaction properties or muscular dystrophy phenotypes in animal models. The exon and flanking intron sequences were subjected to molecular testing by comparative mutation scanning by HT-DHPLC of LGMD patients versus control. We identified a large number of variations in any of the genes in both patients and controls. Correlations with disease or possible modifying effects on the LGMD phenotype remain to be investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Cohort Studies
  • Contractile Proteins / genetics*
  • Filamins
  • Gene Expression Profiling*
  • Genetic Testing / methods*
  • Humans
  • LIM Domain Proteins
  • Membrane Proteins / genetics*
  • Microfilament Proteins / genetics*
  • Muscle Proteins / genetics*
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Mutation / genetics*
  • Phosphopyruvate Hydratase / genetics
  • Sarcoglycans / genetics
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligase Complexes
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Contractile Proteins
  • Filamins
  • KTN1 protein, human
  • LDB3 protein, human
  • LIM Domain Proteins
  • MYOZ1 protein, human
  • MYOZ2 protein, human
  • Membrane Proteins
  • Microfilament Proteins
  • Muscle Proteins
  • NEURL2 protein, human
  • Sarcoglycans
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligase Complexes
  • TRIM11 protein, human
  • TRIM17 protein, human
  • Ubiquitin-Protein Ligases
  • Phosphopyruvate Hydratase