Phenotypic differences of patients with fibrodysplasia ossificans progressive due to p.Arg258Ser variants of ACVR1

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.