Shore Eileen M, Xu Meiqi, Feldman George J, Fenstermacher David A, Cho Tae-Joon, Choi In Ho, Connor J Michael, Delai Patricia, Glaser David L, LeMerrer Martine, Morhart Rolf, Rogers John G, Smith Roger, Triffitt James T, Urtizberea J Andoni, Zasloff Michael, Brown Matthew A, Kaplan Frederick S
Center for Research in FOP and Related Disorders, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Nat Genet. 2006 May;38(5):525-7. doi: 10.1038/ng1783. Epub 2006 Apr 23.
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.
进行性骨化性纤维发育不良（FOP）是一种罕见的常染色体显性疾病，其特征为骨骼畸形和进行性骨外骨化。我们通过连锁分析将FOP定位到2号染色体的2q23-24区域，并在所有受检的患病个体中，于骨形态发生蛋白（BMP）I型受体ACVR1的甘氨酸-丝氨酸（GS）激活域中鉴定出一个相同的杂合突变（617G→A；R206H）。蛋白质建模预测GS域不稳定，这与ACVR1的组成性激活一致，而ACVR1的组成性激活是FOP中异位软骨形成、骨形成和关节融合的潜在原因。
