A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva

被引：884

作者：

Shore, EM

Xu, MQ

Feldman, GJ

Fenstermacher, DA

Brown, MA

Kaplan, FS ^{[1
]}

机构：

[1] Univ Penn, Sch Med, Ctr Res FOP & Related Disorders, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Dept Orthopaed Surg, Philadelphia, PA 19104 USA

[3] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA

[4] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[5] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[6] Univ Penn, Sch Med, Biomed Informat Facil, Philadelphia, PA 19104 USA

[7] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst Canc Immunol & Metab Med, Brisbane, Qld 4102, Australia

[8] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA

来源：

NATURE GENETICS | 2006年 / 38卷 / 05期

关键词：

D O I：

10.1038/ng1783

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

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页码：525 / 527

页数：3

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