title: COL6A1 genomic deletions in Bethlem myopathy and Ullrich muscular dystrophy.
abstract: We have identified highly similar heterozygous COL6A1 genomic deletions, spanning from intron 8 to exon 13 or intron 13, in two patients with Ullrich congenital muscular dystrophy and the milder Bethlem myopathy. The 5' breakpoints of both deletions are located within a minisatellite in intron 8. The mutations cause in-frame deletions of 66 and 84 amino acids in the amino terminus of the triple-helical domain, leading to intracellular accumulation of mutant polypeptides and reduced extracellular collagen VI microfibrils. Our studies identify a deletion-prone region in COL6A1 and suggest that similar mutations can lead to congenital muscle disorders of different clinical severity.
authors.affiliation: Department of Medical and Surgical Critical Care and Center for the Study of Molecular and Clinical Level of Chronic, Degenerative, and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Florence, Italy.
authors.forename: Guglielmina
authors.initials: G
authors.lastname: Pepe
authors.forename: Laura
authors.initials: L
authors.lastname: Lucarini
authors.forename: Rui-Zhu
authors.initials: RZ
authors.lastname: Zhang
authors.forename: Te-Cheng
authors.initials: TC
authors.lastname: Pan
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
authors.forename: Susana
authors.initials: S
authors.lastname: Quijano-Roy
authors.forename: Corine
authors.initials: C
authors.lastname: Gartioux
authors.forename: Katharine M D
authors.initials: KM
authors.lastname: Bushby
authors.forename: Pascale
authors.initials: P
authors.lastname: Guicheney
authors.forename: Mon-Li
authors.initials: ML
authors.lastname: Chu
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D024142:Collagen Type VI / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000235:genetics*; D009136:Muscular Dystrophies / Q000235:genetics*; D009154:Mutation
chemical_list: D024142:Collagen Type VI