title: A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H).
abstract: 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 approximately 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.
authors.affiliation: Department of Neurology, Neuro-Muscular Center, National Omuta Hospital, Fukuoka, Japan. furuya@oomuta.hosp.go.jp
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Furuya
authors.forename: Koji
authors.initials: K
authors.lastname: Ikezoe
authors.forename: Lixiang
authors.initials: L
authors.lastname: Wang
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ohyagi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Motomura
authors.forename: Naoki
authors.initials: N
authors.lastname: Fujii
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kira
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fukumaki
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009221:Myositis Ossificans / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D017386:Sequence Homology, Amino Acid
chemical_list: C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I