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A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H)
Author(s) -
Furuya Hirokazu,
Ikezoe Koji,
Wang Lixiang,
Ohyagi Yasumasa,
Motomura Kyoko,
Fujii Naoki,
Kira Junichi,
Fukumaki Yasuyuki
Publication year - 2008
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.32151
Subject(s) - fibrodysplasia ossificans progressiva , medicine , heterotopic ossification , mutation , mutation testing , endochondral ossification , genetics , biology , gene , surgery , anatomy , cartilage
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disease characterized by progressive heterotopic endochondral osteogenesis with great‐toe malformations. A 617G > A (R206H) mutation of the activin A type 1 receptor gene ( ACVR1 ) has been found in all previously reported patients with FOP. Thus, this is one of the most specific of all disease‐associated mutations. We report here on a 62‐year‐old man with slowly progressive FOP and a novel mutation in ACVR1 . He developed difficulty in moving his shoulder since age 10 years due to contraction of the shoulder joint. The symptoms progressed slowly, and he could not walk at age 36 years and was bedridden at 55 years. He also showed rigid spine, baldness, sensorineural hearing loss, and hypodactyly accompanied by abnormal ectopic ossification. Analysis of ACVR1 and its cDNA revealed that the patient is heterozygous for a mutation, 1067G > A (G356D). Typing of SNPs located in the ∼0.5‐Mb region spanning ACVR1 and its neighbor genes suggested that 1067G > A is a de novo mutation. These results give a clue to better understanding of FOP as well as of the mild clinical symptoms in the patient. © 2008 Wiley‐Liss, Inc.