Human desmin gene: cDNA sequence, regional localization and exclusion of the locus in a familial desmin-related myopathy

Hum Genet. 1996 Oct;98(4):422-9. doi: 10.1007/s004390050233.

Abstract

Desmin is a muscle-specific intermediate filament that is encoded by a gene assigned to human chromosome 2q35. Desmin-related myopathies are inherited disorders characterized by an intrasarcoplasmic accumulation of desmin. Recently, the knockout of the desmin gene was shown to generate a myopathic syndrome in transgenic mice, suggesting that functional abnormality of desmin may generate similar clinical symptoms in mouse and human. To determine the potential role of the desmin gene in a well-defined desmin-related myopathy (autosomal dominant form of Fardeau), human desmin cDNAs obtained from affected and unaffected individuals were cloned, sequenced and compared. No obvious mutation was detected. A BssHII restriction fragment length polymorphism (RFLP) was identified in exon 6 of the desmin gene. This RFLP was associated with a previously identified EcoRV RFLP in exon 4 to generate a tetra-allelic system, which was tested for linkage to the desmin-related myopathy in three families. The human desmin gene was localized within an 11-cM interval on chromosome 2q using a panel of radiation hybrids. This 11-cM region was clearly excluded by linkage analysis in the three desmin-related myopathy families using a set of highly polymorphic microsatellite markers. These results suggest that the desmin gene is not primarily involved in this disease.

Publication types

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

MeSH terms

  • Alternative Splicing
  • Animals
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 2*
  • DNA Primers
  • DNA, Complementary
  • Deoxyribonucleases, Type II Site-Specific
  • Desmin / genetics*
  • Exons
  • Female
  • Genetic Linkage
  • Genotype
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Muscular Diseases / genetics*
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length*
  • Recombination, Genetic

Substances

  • DNA Primers
  • DNA, Complementary
  • Desmin
  • Deoxyribonucleases, Type II Site-Specific
  • GATATC-specific type II deoxyribonucleases

Associated data

  • GENBANK/M58168
  • GENBANK/U59167