Autosomal recessive myosclerosis myopathy is a collagen VI disorder.
OBJECTIVE
To determine the clinical and molecular features of a new phenotype related to collagen VI myopathies.


METHODS
We examined two patients belonging to a consanguineous family affected by myosclerosis myopathy, screened for mutations of collagen VI genes, and performed a detailed biochemical and morphologic analysis of the muscle biopsy and cultured fibroblasts.


RESULTS
The patients had a novel homozygous nonsense COL6A2 mutation (Q819X); the mutated messenger RNA escaped nonsense-mediated decay and was translated into a truncated alpha2(VI) chain, lacking the sole C2 domain. The truncated chain associated with the other two chains, giving rise to secreted collagen VI. Monomers containing the truncated chain were assembled into dimers, but tetramers were almost absent; secreted collagen VI was quantitatively reduced and structurally abnormal in cultured fibroblasts. Mutated collagen did not correctly localize in the basement membrane of muscle fibers and was absent in the capillary wall. Ultrastructural analysis of muscle showed an unusual combination of basement membrane thickening and duplication, and increased number of pericytes.


CONCLUSIONS
This familial case has the characteristic features of myosclerosis myopathy and carries a homozygous COL6A2 mutation responsible for a peculiar pattern of collagen VI defects. Our study demonstrates that myosclerosis myopathy should be considered a collagen VI disorder allelic to Ullrich congenital muscular dystrophy and Bethlem myopathy.
Department of Experimental and Diagnostic Medicine, University of Ferrara, Italy.
L
L
Merlini
E
E
Martoni
P
P
Grumati
P
P
Sabatelli
S
S
Squarzoni
A
A
Urciuolo
A
A
Ferlini
F
F
Gualandi
P
P
Bonaldo
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001706:Biopsy; D002478:Cells, Cultured; D003095:Collagen Diseases / Q000151:congenital* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D024142:Collagen Type VI / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009135:Muscular Diseases / Q000151:congenital* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D017354:Point Mutation
D024142:Collagen Type VI