title: Human desmin gene: cDNA sequence, regional localization and exclusion of the locus in a familial desmin-related myopathy.
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.
authors.affiliation: Université Paris VII, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Vicart
authors.forename: J M
authors.initials: JM
authors.lastname: Dupret
authors.forename: J
authors.initials: J
authors.lastname: Hazan
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Gyapay
authors.forename: R
authors.initials: R
authors.lastname: Krishnamoorthy
authors.forename: J
authors.initials: J
authors.lastname: Weissenbach
authors.forename: M
authors.initials: M
authors.lastname: Fardeau
authors.forename: D
authors.initials: D
authors.lastname: Paulin
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D017931:DNA Primers; D018076:DNA, Complementary; D015252:Deoxyribonucleases, Type II Site-Specific; D003893:Desmin / Q000235:genetics*; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011995:Recombination, Genetic
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D003893:Desmin; D015252:Deoxyribonucleases, Type II Site-Specific; C027440:GATATC-specific type II deoxyribonucleases