Mutations of COL10A1 in schmid metaphyseal chondrodysplasia
Mutations of COL10A1 in schmid metaphyseal chondrodysplasia
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DOI：
10.1002/humu.20183
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发表时间：
2005-06-01
期刊：
影响因子：
3.9
通讯作者：
Savarirayan, R
中科院分区：
文献类型：
--
作者：
Bateman, JF;Wilson, R;Savarirayan, R
施密德干骺端软骨发育不良（SMCD）是一种显性遗传性软骨疾病，由肥大软骨细胞外基质结构蛋白胶原X（COL 10A 1）基因突变引起。已经描述了30个杂合突变，大约平均分为两种突变类型，错义突变和引入提前终止信号的突变。COL 10A 1突变聚集（33/36）在外显子3的3'区，其编码C-末端NC 1三聚化结构域。COL 10A 1错义突变的影响已经通过体外表达和组装测定以及细胞转染研究进行了研究，这表明一个常见的结果是胶原X三聚体和分泌的破坏，随之而来的是细胞内降解。已经在两名患者中检查了软骨组织中COL 10A 1无义突变的效果，证明突变mRNA通过无义介导的mRNA衰变被完全去除。因此，对于这两类突变，功能性单倍不足是SMCD临床表型的最可能原因。(c)2005 Wiley-Liss，Inc.
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. (c) 2005 Wiley-Liss, Inc.