Human Genetics

, Volume 98, Issue 4, pp 422–429

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

  • P. Vicart
  • Jean-Marie Dupret
  • Jamilé Hazan
  • Zhenlin Li
  • Gabor Gyapay
  • Rajagopal Krishnamoorthy
  • Jean Weissenbach
  • Michel Fardeau
  • Denise Paulin
Original investigation

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.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • P. Vicart
    • 1
  • Jean-Marie Dupret
    • 1
  • Jamilé Hazan
    • 2
  • Zhenlin Li
    • 1
  • Gabor Gyapay
    • 2
  • Rajagopal Krishnamoorthy
    • 3
  • Jean Weissenbach
    • 2
  • Michel Fardeau
    • 4
  • Denise Paulin
    • 1
  1. 1.Université Paris VII and SCME Institut Pasteur, 25 rue du Dr Roux, F-75015 Paris, France Tel.: +33-1-45-68-84-93; Fax: +33-1-45-68-86-81FR
  2. 2.CNRS URA1922, Généthon, 1 rue de l’Internationale, F- 91000 Evry, FranceFR
  3. 3.INSERM U120, Hôpital Robert Debré, 48 Bd Sérurier, F-75019 Paris, FranceFR
  4. 4.INSERM U153, 17 rue du Fer à Moulin, F-75005 Paris, FranceFR

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