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PubMed:20106987 JSONTXT 29 Projects

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Id Subject Object Predicate Lexical cue
T1 0-120 Sentence denotes Recessive COL6A2 C-globular missense mutations in Ullrich congenital muscular dystrophy: role of the C2a splice variant.
T2 121-295 Sentence denotes Ullrich congenital muscular dystrophy (UCMD) is a disabling and life-threatening disorder resulting from either recessive or dominant mutations in genes encoding collagen VI.
T3 296-495 Sentence denotes Although the majority of the recessive UCMD cases have frameshift or nonsense mutations in COL6A1, COL6A2, or COL6A3, recessive structural mutations in the COL6A2 C-globular region are emerging also.
T4 496-563 Sentence denotes However, the underlying molecular mechanisms have remained elusive.
T5 564-708 Sentence denotes Here we identified a homozygous COL6A2 E624K mutation (C1 subdomain) and a homozygous COL6A2 R876S mutation (C2 subdomain) in two UCMD patients.
T6 709-849 Sentence denotes The consequences of the mutations were investigated using fibroblasts from patients and cells stably transfected with the mutant constructs.
T7 850-1065 Sentence denotes In contrast to expectations based on the clinical severity of these two patients, secretion and assembly of collagen VI were moderately affected by the E624K mutation but severely impaired by the R876S substitution.
T8 1066-1293 Sentence denotes The E624K substitution altered the electrostatic potential of the region surrounding the metal ion-dependent adhesion site, resulting in a collagen VI network containing thick fibrils and spots with densely packed microfibrils.
T9 1294-1391 Sentence denotes The R876S mutation prevented the chain from assembling into triple-helical collagen VI molecules.
T10 1392-1580 Sentence denotes The minute amount of collagen VI secreted by the R876S fibroblasts was solely composed of a faster migrating chain corresponding to the C2a splice variant with an alternative C2 subdomain.
T11 1581-1671 Sentence denotes In transfected cells, the C2a splice variant was able to assemble into short microfibrils.
T12 1672-1839 Sentence denotes Together, the results suggest that the C2a splice variant may functionally compensate for the loss of the normal COL6A2 chain when mutations occur in the C2 subdomain.