title: Two related Dutch families with a clinically variable presentation of cardioskeletal myopathy caused by a novel S13F mutation in the desmin gene.
abstract: Desmin-related myopathy is characterised by skeletal muscle weakness often combined with cardiac involvement. Mutations in the desmin gene have been described as a cause of desmin-related myopathy (OMIM 601419). We report here on two distantly related Dutch families with autosomal dominant inheritance of desmin-related myopathy affecting 15 family members. A highly heterogeneous clinical picture is apparent, varying from isolated dilated cardiomyopathy to a more generalised skeletal myopathy and mild respiratory problems. Morphological analysis of muscle biopsies revealed intracytoplasmic desmin aggregates (desmin and p62 staining). In both families we identified an identical novel pathogenic heterozygous missense mutation, S13F, in the 'head' domain of the desmin gene which cosegregates with the disease phenotype. This is the 5th reported missense mutation located at the 'head' domain of the desmin gene and the first reported Dutch family with desmin-related myopathy. This article illustrates the importance of analysing the desmin gene in patients with (familial) cardiac conduction disease, dilated cardiomyopathy and/or a progressive skeletal myopathy resembling limb-girdle muscular dystrophy.
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, Post Box 30001, 9700 RB Groningen, The Netherlands. j.e.h.bergman@medgen.umcg.nl
authors.forename: Jorieke E H
authors.initials: JE
authors.lastname: Bergman
authors.forename: Hermine E
authors.initials: HE
authors.lastname: Veenstra-Knol
authors.forename: Anthonie J
authors.initials: AJ
authors.lastname: van Essen
authors.forename: Conny M A
authors.initials: CM
authors.lastname: van Ravenswaaij
authors.forename: Wilfred F A
authors.initials: WF
authors.lastname: den Dunnen
authors.forename: Arthur
authors.initials: A
authors.lastname: van den Wijngaard
authors.forename: J Peter
authors.initials: JP
authors.lastname: van Tintelen
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003893:Desmin / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020125:Mutation, Missense; D009426:Netherlands; D010375:Pedigree; D010641:Phenotype
chemical_list: D003893:Desmin