title: Detection of common and private mutations in the COL6A1 gene of patients with Bethlem myopathy.
abstract: BACKGROUND
  Dominant mutations in COL6A1, COL6A2, and COL6A3, the three genes encoding collagen type VI, a ubiquitous extracellular matrix protein, are associated with Bethlem myopathy (BM) and Ullrich scleroatonic muscular dystrophy.
  
  
  METHODS
  The authors devised a method to screen the entire coding sequence of the three genes by reverse transcriptase-PCR amplification of total RNA from skin fibroblasts and direct sequencing of the resulting 25 overlapping cDNA fragments covering 107 exons.
  
  
  RESULTS
  Four splicing and four missense mutations were identified in 16 patients with BM, six of which are novel mutations in COL6A1. Both common and private mutations are localized in the alpha1 (VI) chain between the regions corresponding to the 3' end of the NH2-globular domain and the 5' end of the triple helix, encoded by exons 3 through 14.
  
  
  CONCLUSIONS
  The clustering of the mutations in a relatively narrow area of the three collagen type VI chains in patients with Bethlem myopathy (BM) suggests that mutations in different regions could result in different phenotypes or in no phenotype at all. Moreover, the detection of mutations in only 60% of the patients suggests the existence of at least another gene associated with BM. The authors propose the direct sequencing of COL6 cDNAs as the first mutation screening analysis in BM, given the high number of exon-skipping events.
authors.affiliation: Department of Medical and Surgical Critical Care, Center of Research, Transfer and High Education, MCIDNENT, University of Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Lucioli
authors.forename: B
authors.initials: B
authors.lastname: Giusti
authors.forename: E
authors.initials: E
authors.lastname: Mercuri
authors.forename: O Camacho
authors.initials: OC
authors.lastname: Vanegas
authors.forename: L
authors.initials: L
authors.lastname: Lucarini
authors.forename: V
authors.initials: V
authors.lastname: Pietroni
authors.forename: A
authors.initials: A
authors.lastname: Urtizberea
authors.forename: R
authors.initials: R
authors.lastname: Ben Yaou
authors.forename: M
authors.initials: M
authors.lastname: de Visser
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Kooi
authors.forename: C
authors.initials: C
authors.lastname: Bönnemann
authors.forename: S T
authors.initials: ST
authors.lastname: Iannaccone
authors.forename: L
authors.initials: L
authors.lastname: Merlini
authors.forename: K
authors.initials: K
authors.lastname: Bushby
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
authors.forename: E
authors.initials: E
authors.lastname: Bertini
authors.forename: M-L
authors.initials: ML
authors.lastname: Chu
authors.forename: G
authors.initials: G
authors.lastname: Pepe
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D024142:Collagen Type VI / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D021122:Protein Subunits / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics
chemical_list: D024142:Collagen Type VI; D021122:Protein Subunits; D012333:RNA, Messenger