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Mutations of COL10A1 in Schmid metaphyseal chondrodysplasia
Author(s) -
Bateman John F.,
Wilson Richard,
Freddi Susanna,
Lamandé Shireen R.,
Savarirayan Ravi
Publication year - 2005
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20183
Subject(s) - missense mutation , biology , nonsense mutation , haploinsufficiency , mutation , genetics , mutant , microbiology and biotechnology , cartilage , exon , phenotype , gene , anatomy
Schmid metaphyseal chondrodysplasia (SMCD) is a dominantly inherited cartilage disorder caused by mutations in the gene for the hypertrophic cartilage extracellular matrix structural protein, collagen X ( COL10A1 ). Thirty heterozygous mutations have been described, about equally divided into two mutation types, missense mutations, and mutations that introduce premature termination signals. The COL10A1 mutations are clustered (33/36) in the 3′ region of exon 3, which codes for the C‐terminal NC1 trimerization domain. The effect of COL10A1 missense mutations have been examined by in vitro expression and assembly assays and cell transfection studies, which suggest that a common consequence is the disruption of collagen X trimerization and secretion, with consequent intracellular degradation. The effect of COL10A1 nonsense mutations in cartilage tissue has been examined in two patients, demonstrating that the mutant mRNA is completely removed by nonsense mediated mRNA decay. Thus for both classes of mutations, functional haploinsufficiency is the most probable cause of the clinical phenotype in SMCD. Hum Mutat 25:525–534, 2005. © 2005 Wiley‐Liss, Inc.

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