title: Autosomal recessive inheritance of classic Bethlem myopathy.
abstract: Mutations in the collagen VI genes (COL6A1, COL6A2 and COL6A3) result in Ullrich congenital muscular dystrophy (CMD), Bethlem myopathy or phenotypes intermediate between Ullrich CMD and Bethlem myopathy. While Ullrich CMD can be caused by either recessively or dominantly acting mutations, Bethlem myopathy has thus far been described as an exclusively autosomal dominant condition. We report two adult siblings with classic Bethlem myopathy who are compound heterozygous for a single nucleotide deletion (exon 23; c.1770delG), leading to in-frame skipping of exon 23 on the maternal allele, and a missense mutation p.R830W in exon 28 on the paternal allele. The parents are carriers of the respective mutations and are clinically unaffected. The exon skipping mutation in exon 23 results in a chain incapable of heterotrimeric assembly, while p.R830W likely ameliorates the phenotype into the Bethlem range. Thus, autosomal recessive inheritance can also underlie Bethlem myopathy, supporting the notion that Ullrich CMD and Bethlem myopathy are part of a common clinical and genetic spectrum.
authors.affiliation: Division of Neurology, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: A Reghan
authors.initials: AR
authors.lastname: Foley
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Yaqun
authors.initials: Y
authors.lastname: Zou
authors.forename: Alexandra
authors.initials: A
authors.lastname: Columbus
authors.forename: John
authors.initials: J
authors.lastname: Shoffner
authors.forename: Diane M
authors.initials: DM
authors.lastname: Dunn
authors.forename: Robert B
authors.initials: RB
authors.lastname: Weiss
authors.forename: Carsten G
authors.initials: CG
authors.lastname: Bönnemann
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D024142:Collagen Type VI / Q000235:genetics*; D020405:Dermis / Q000378:metabolism; D005091:Exons; D005347:Fibroblasts / Q000378:metabolism; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
chemical_list: C504344:COL6A2 protein, human; D024142:Collagen Type VI