A recurrent mutation c.617G>A in the ACVR1 gene causes fibrodysplasia ossificans progressiva in two Chinese patients

Calcif Tissue Int. 2009 May;84(5):361-5. doi: 10.1007/s00223-009-9235-9. Epub 2009 Mar 20.

Abstract

Fibrodysplasia ossificans progressiva (FOP; OMIM 135100) is a rare heritable disorder of connective tissue characterized by congenital malformations of the great toes and recurrent episodes of painful soft tissue swelling that lead to heterotopic ossifications. Recent studies have shown that the ACVR1 (activin A receptor, type I; OMIM 102576) gene, which encodes the BMP type I receptor protein, is responsible for this disease. We observed two Chinese patients who suffered from progressive pain and ankylosis of major joints with congenital bilateral hallus valgus malformation, neck stiffness, and several posttraumatic ossified lesions on the head and dorsum. Both patients were diagnosed as having FOP. This study aimed to investigate the ACVR1 gene mutation in Chinese FOP patients. Direct sequence analysis of genomic DNA and restriction enzyme digestion demonstrated the presence of a single heterozygous c.617G>A (p.R206H) mutation in the ACVR1 gene in both patients. This mutation is first reported in Chinese patients with FOP and it was de novo in both affected families.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I / genetics*
  • Adolescent
  • Age of Onset
  • Amino Acid Substitution / genetics
  • Asians / genetics
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology
  • Bone and Bones / physiopathology
  • DNA Mutational Analysis
  • Disease Progression
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genotype
  • Heterozygote
  • Humans
  • Male
  • Mutation, Missense / genetics*
  • Myositis Ossificans / genetics*
  • Myositis Ossificans / pathology
  • Myositis Ossificans / physiopathology

Substances

  • Genetic Markers
  • ACVR1 protein, human
  • Activin Receptors, Type I