Effects on Collagen VI mrna Stability and Microfibrillar Assembly of Three COL6A2 Mutations in Two Families with Ullrich Congenital Muscular Dystrophy (Articolo in rivista)

Type
Label
  • Effects on Collagen VI mrna Stability and Microfibrillar Assembly of Three COL6A2 Mutations in Two Families with Ullrich Congenital Muscular Dystrophy (Articolo in rivista) (literal)
Anno
  • 2002-01-01T00:00:00+01:00 (literal)
Alternative label
  • Zhu Zhang R.1, Sabatelli P.2, Cheng Pan T.1, Squarzoni S.2, Mattioli E.3, Bertini E.4, Pepe G.5, Li Chu M.1-6 (2002)
    Effects on Collagen VI mrna Stability and Microfibrillar Assembly of Three COL6A2 Mutations in Two Families with Ullrich Congenital Muscular Dystrophy
    (literal)
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  • Zhu Zhang R.1, Sabatelli P.2, Cheng Pan T.1, Squarzoni S.2, Mattioli E.3, Bertini E.4, Pepe G.5, Li Chu M.1-6 (literal)
Pagina inizio
  • 43557 (literal)
Pagina fine
  • 43564 (literal)
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  • Lavoro a carattere interdisciplinare di tipo clinico con collaborazioni internazionali. Lavoro rendicontato per il progetto europeo MYOCLUSTER I.F. 7,258 (literal)
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  • 277 (literal)
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  • I.F. 7,258 (literal)
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  • We recently reported a severe deficiency in collagen type VI, resulting from recessive mutations of the COL6A2 gene, in patients with Ullrich congenital muscular dystrophy. Their parents, who are all carriers of one mutant allele, are unaffected, although heterozygous mutations in collagen VI caused Bethlem myopathy. Here we investigated the consequences of three COL6A2 mutations in fibroblasts from patients and their parents in two Ullrich families. All three mutations lead to nonsense-mediated mRNA decay. However, very low levels of undegraded mutant mRNA remained in patient B with compound heterozygous mutations at the distal part of the triple-helical domain, resulting in deposition of abnormal microfibrils that cannot form extensive networks. This observation suggests that the C- terminal globular domain is not essential for triple-helix formation but is critical for microfibrillar assembly. In all parents, the COL6A2 mRNA levels are reduced to 57-73% of the control, but long term collagen VI matrix depositions are comparable with that of the control. The almost complete absence of abnormal protein and near-normal accumulation of microfibrils in the parents may account for their lack of myopathic symptoms (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • 1Department of Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, 2Institute of Normal and Pathological Cytomorphology, CNR 3Neuromuscular Unit, IOR, Bologna 4Department of Neurosciences, Molecular Medicine, \"Bambino Gesù Hospital, Roma 5Department of Medical and Surgical Critical Care, Uni. Firenze 6Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia (literal)
Titolo
  • Effects on Collagen VI mrna Stability and Microfibrillar Assembly of Three COL6A2 Mutations in Two Families with Ullrich Congenital Muscular Dystrophy (literal)
Abstract
  • We recently reported a severe deficiency in collagen type VI, resulting from recessive mutations of the COL6A2 gene, in patients with Ullrich congenital muscular dystrophy. Their parents, who are all carriers of one mutant allele, are unaffected, although heterozygous mutations in collagen VI caused Bethlem myopathy. Here we investigated the consequences of three COL6A2 mutations in fibroblasts from patients and their parents in two Ullrich families. All three mutations lead to nonsense-mediated mRNA decay. However, very low levels of undegraded mutant mRNA remained in patient B with compound heterozygous mutations at the distal part of the triple-helical domain, resulting in deposition of abnormal microfibrils that cannot form extensive networks. This observation suggests that the C- terminal globular domain is not essential for triple-helix formation but is critical for microfibrillar assembly. In all parents, the COL6A2 mRNA levels are reduced to 57-73% of the control, but long term collagen VI matrix depositions are comparable with that of the control. The almost complete absence of abnormal protein and near-normal accumulation of microfibrils in the parents may account for their lack of myopathic symptoms. (literal)
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