title: Phenotypic differences of patients with fibrodysplasia ossificans progressive due to p.Arg258Ser variants of ACVR1.
abstract: Fibrodysplasia ossificans progressiva (FOP) is a rare, congenital disorder caused by heterozygous mutation of the bone morphogenetic protein type I receptor ACVR1. Various forms of atypical FOP have recently been identified, and a recurrent mutation, ACVR1 (p.Arg258Ser) was reported. We encountered a 17-year-old Japanese female patient with sporadic occurrence of FOP. At the age of 7 years, radiological examination revealed progressive heterotopic ossification and cervical spine malformations. Although great toe malformation was not observed, we diagnosed her as having FOP. Then, ACVR1 was analyzed and a recurrent mutation of p.Arg258Ser was identified. We noticed that there may be phenotypic differences between c.774G>T and c.774G>C, which lead to the same amino-acid change, p.Arg258Ser. Genotype-phenotype correlation was discussed with the review of the previous reports.
authors.affiliation: Department of Rehabilitation Medicine, The University of Tokyo Hospital , Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Nakahara
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine , Tokyo, Japan.
authors.forename: Ryuyo
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan; Project of Clinical and Basic Research for FOP at Saitama Medical University, Saitama, Japan.
authors.forename: Takenobu
authors.initials: T
authors.lastname: Katagiri
authors.affiliation: Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan; Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan; Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Toguchida
authors.affiliation: Department of Rehabilitation Medicine, The University of Tokyo Hospital , Tokyo, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Haga