A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva
A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva
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DOI：
10.1038/ng1783
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发表时间：
2006-05-01
期刊：
影响因子：
30.8
通讯作者：
Kaplan, FS
中科院分区：
文献类型：
--
作者：
Shore, EM;Xu, MQ;Kaplan, FS
进行性骨化性纤维发育不良（FOP）是一种罕见的骨骼畸形和进行性骨外骨化的常染色体显性遗传病。我们通过连锁分析将FOP定位到染色体2 q23 -24，并在所有受检个体中鉴定出ACVR 1（BMP I型受体）的甘氨酸-丝氨酸（GS）激活域中的相同杂合突变（617 G-> A; R206 H）。蛋白质建模预测GS结构域的不稳定，与ACVR 1的组成性激活一致，ACVR 1是FOP中所见的异位软骨形成、骨形成和关节融合的根本原因。
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. We mapped FOP to chromosome 2q23-24 by linkage analysis and identified an identical heterozygous mutation (617G -> A; R206H) in the glycine-serine (GS) activation domain of ACVR1, a BMP type I receptor, in all affected individuals examined. Protein modeling predicts destabilization of the GS domain, consistent with constitutive activation of ACVR1 as the underlying cause of the ectopic chondrogenesis, osteogenesis and joint fusions seen in FOP.