Reduced collagen VI causes Bethlem myopathy: a heterozygous COL6A1 nonsense mutation results in mRNA decay and functional haploinsufficiency.
Hum Mol Genet
; 7(6): 981-9, 1998 Jun.
Article
en En
| MEDLINE
| ID: mdl-9580662
ABSTRACT
We have identified a new pathogenic mechanism for an inherited muscular dystrophy in which functional haploinsufficiency of the extracellular matrix protein collagen VI causes Bethlem myopathy. The heterozygous COL6A1 mutation results in a single base deletion from the mRNA and a premature stop codon. The mutant mRNA is unstable, subject to nonsense-mediated mRNA decay, and is almost completely absent both from patient fibroblasts and skeletal muscle, resulting in haploinsufficiency of the alpha1(VI) subunit and reduced production of structurally normal collagen VI. This is the first example of a muscular dystrophy caused by haploinsufficiency of a structural protein or member of the dystrophin-glycoprotein complex, and identifies collagen VI as a critical contributor to cell-matrix adhesion in skeletal muscle.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ARN Mensajero
/
Colágeno
/
Mutación Puntual
/
Distrofias Musculares
Tipo de estudio:
Etiology_studies
Límite:
Humans
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
1998
Tipo del documento:
Article
País de afiliación:
Australia