Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin

Nat Genet. 2000 Feb;24(2):163-6. doi: 10.1038/72822.

Abstract

Autosomal recessive limb-girdle muscular dystrophies (AR LGMDs) are a genetically heterogeneous group of disorders that affect mainly the proximal musculature. There are eight genetically distinct forms of AR LGMD, LGMD 2A-H (refs 2-10), and the genetic lesions underlying these forms, except for LGMD 2G and 2H, have been identified. LGMD 2A and LGMD 2B are caused by mutations in the genes encoding calpain 3 (ref. 11) and dysferlin, respectively, and are usually associated with a mild phenotype. Mutations in the genes encoding gamma-(ref. 14), alpha-(ref. 5), beta-(refs 6,7) and delta (ref. 15)-sarcoglycans are responsible for LGMD 2C to 2F, respectively. Sarcoglycans, together with sarcospan, dystroglycans, syntrophins and dystrobrevin, constitute the dystrophin-glycoprotein complex (DGC). Patients with LGMD 2C-F predominantly have a severe clinical course. The LGMD 2G locus maps to a 3-cM interval in 17q11-12 in two Brazilian families with a relatively mild form of AR LGMD (ref. 9). To positionally clone the LGMD 2G gene, we constructed a physical map of the 17q11-12 region and refined its localization to an interval of 1.2 Mb. The gene encoding telethonin, a sarcomeric protein, lies within this candidate region. We have found that mutations in the telethonin gene cause LGMD 2G, identifying a new molecular mechanism for AR LGMD.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 17*
  • Connectin
  • Exons
  • Female
  • Genes, Recessive
  • Genetic Markers
  • Humans
  • Introns
  • Male
  • Microsatellite Repeats
  • Molecular Sequence Data
  • Muscle Proteins / chemistry
  • Muscle Proteins / genetics*
  • Muscular Dystrophies / classification
  • Muscular Dystrophies / genetics*
  • Nuclear Family
  • Pedigree
  • Promoter Regions, Genetic
  • Sarcomeres / genetics
  • Sarcomeres / metabolism
  • Sequence Alignment

Substances

  • Connectin
  • Genetic Markers
  • Muscle Proteins
  • TCAP protein, human

Associated data

  • GENBANK/AC002346
  • GENBANK/AC003103
  • GENBANK/AC003976
  • GENBANK/AC004134
  • GENBANK/AC004675
  • GENBANK/AC005288
  • GENBANK/AC005919
  • GENBANK/AC006237
  • GENBANK/AC007776
  • GENBANK/AC009283
  • GENBANK/AJ010063
  • GENBANK/AJ011098
  • GENBANK/G62211
  • GENBANK/G62213
  • GENBANK/G62214

Grant support