A mutation in the variable repeat region of the aggrecan gene (AGC1) causes a form of spondyloepiphyseal dysplasia associated with severe, premature osteoarthritis
A mutation in the variable repeat region of the aggrecan gene (AGC1) causes a form of spondyloepiphyseal dysplasia associated with severe, premature osteoarthritis
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DOI：
10.1086/444401
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发表时间：
2005-09-01
影响因子：
9.8
通讯作者：
Wallis, G
中科院分区：
文献类型：
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作者：
Gleghorn, L;Ramesar, R;Wallis, G
脊椎骨骺发育不良（SED）包括一组以躯干和四肢缩短为特征的异质性疾病。常染色体显性 SED 型 Kimberley (SEDK) 与过早退行性关节病相关，之前已在多代家族中定位到 15q26.1 上的一个新基因座。该基因座包含基因 AGC1，它编码聚集蛋白聚糖，这是最丰富的软骨蛋白多糖的核心蛋白。我们筛选了 AGC1 的突变，并在 SEDK 家族受影响个体的外显子 12 的可变重复区域内鉴定了单碱基对插入，该插入引入了 212 个氨基酸的移码，包括 22 个半胱氨酸残基，随后是提前终止密码子。这是首次鉴定出导致人类疾病的 AGC1 突变。这一发现扩展了可能导致 SED 的突变基因范围，因此将有助于对这组复杂病症进行分子描述。
Spondyloepiphyseal dysplasia (SED) encompasses a heterogeneous group of disorders characterized by shortening of the trunk and limbs. The autosomal dominant SED type Kimberley (SEDK) is associated with premature degenerative arthropathy and has been previously mapped in a multigenerational family to a novel locus on 15q26.1. This locus contains the gene AGC1, which encodes aggrecan, the core protein of the most abundant proteoglycan of cartilage. We screened AGC1 for mutations and identified a single-base-pair insertion, within the variable repeat region of exon 12 in affected individuals from the family with SEDK, that introduces a frameshift of 212 amino acids, including 22 cysteine residues, followed by a premature stop codon. This is the first identification of an AGC1 mutation causing a human disorder. This finding extends the spectrum of mutated genes that may cause SED and thus will aid in the molecular delineation of this complex group of conditions.