title: Dominant and recessive COL6A1 mutations in Ullrich scleroatonic muscular dystrophy.
abstract: In this study, we characterized five Ullrich scleroatonic muscular dystrophy patients (two Italians, one Belgian, and two Turks) with a clinical phenotype showing different degrees of severity, all carrying mutations localized in COL6A1. We sequenced the three entire COL6 complementary DNA. Three of five patients have recessive mutations: two patients (P1and P3) have homozygous single-nucleotide deletions, one in exon 9 and one in exon 22; one patient (P2) has a homozygous single-nucleotide substitution leading to a premature termination codon in exon 31. The nonsense mutation of P2 also causes a partial skipping of exon 31 with the formation of a premature termination codon in exon 32 in 15% of the total COL6A1 messenger RNA. The remaining two patients carry a heterozygous glycine substitution in exons 9 and 10 inside the triple-helix region; both are dominant mutations because the missense mutations are absent in the DNA of their respective parents. As for the three homozygous recessive mutations, the apparently healthy consanguineous parents all carry a heterozygous mutated allele. Here, for the first time, we report a genotype-phenotype correlation demonstrating that heterozygous glycine substitutions in the triple-helix domain of COL6A1 are dominant and responsible for a milder Ullrich scleroatonic muscular dystrophy phenotype, and that recessive mutations in COL6A1 correlate with more severe clinical and biochemical Ullrich scleroatonic muscular dystrophy phenotypes.
authors.affiliation: Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy.
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
authors.forename: Laura
authors.initials: L
authors.lastname: Lucarini
authors.forename: Valentina
authors.initials: V
authors.lastname: Pietroni
authors.forename: Simona
authors.initials: S
authors.lastname: Lucioli
authors.forename: Brunella
authors.initials: B
authors.lastname: Bandinelli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sabatelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Squarzoni
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrini
authors.forename: Corine
authors.initials: C
authors.lastname: Gartioux
authors.forename: Beril
authors.initials: B
authors.lastname: Talim
authors.forename: Filip
authors.initials: F
authors.lastname: Roelens
authors.forename: Luciano
authors.initials: L
authors.lastname: Merlini
authors.forename: Haluk
authors.initials: H
authors.lastname: Topaloglu
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Pascale
authors.initials: P
authors.lastname: Guicheney
authors.forename: Guglielmina
authors.initials: G
authors.lastname: Pepe
mesh_terms: D000293:Adolescent; D015152:Blotting, Northern; D015153:Blotting, Western / Q000379:methods; D002648:Child; D002675:Child, Preschool; D024142:Collagen Type VI / Q000235:genetics* / Q000378:metabolism; D003240:Connective Tissue Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003599:Cytoskeleton / Q000648:ultrastructure; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D005091:Exons; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique / Q000379:methods; D005808:Genes, Recessive; D005998:Glycine / Q000235:genetics; D006801:Humans; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D008970:Molecular Weight; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D044465:White People
chemical_list: D024142:Collagen Type VI; D018076:DNA, Complementary; D012333:RNA, Messenger; D005998:Glycine