Collagen expression in fibroblasts with a novel LMNA mutation.
Laminopathies are a group of genetic disorders caused by LMNA mutations; they include muscular dystrophies, lipodystrophies, and progeroid syndromes. We identified a novel heterozygous LMNA mutation, L59R, in a patient with the general appearance of mandibuloacral dysplasia and progeroid features. Examination of the nuclei of dermal fibroblasts revealed the irregular morphology characteristic of LMNA mutant cells. The nuclear morphological abnormalities of LMNA mutant lymphoblastoid cell lines were less prominent compared to those of primary fibroblasts. Since it has been reported that progeroid features are associated with increased extracellular matrix in dermal tissues, we compared a subset of these components in fibroblast cultures from LMNA mutants with those of control fibroblasts. There was no evidence of intracellular accumulation or altered mobility of collagen chains, or altered conversion of procollagen to collagen, suggesting that skin fibroblast-mediated matrix production may not play a significant role in the pathogenesis of this particular laminopathy.
Nguyen
Desiree
D
Department of Pathology, University of Washington, Seattle, WA 98195, USA.
Leistritz
Dru F
DF
Turner
Lesley
L
MacGregor
David
D
Ohson
Kamal
K
Dancey
Paul
P
Martin
George M
GM
Oshima
Junko
J
D000293:Adolescent; D002478:Cells, Cultured; D003057:Cockayne Syndrome / Q000235:genetics* / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D034904:Lamin Type A / Q000235:genetics*; D008060:Lipodystrophy / Q000235:genetics / Q000378:metabolism; D009154:Mutation
D024042:Collagen Type I; D024061:Collagen Type III; C494847:LMNA protein, human; D034904:Lamin Type A