Confirmation of the recurrent ACVR1 617G>A mutation in South Africans with fibrodysplasia ossificans progressiva

Abstract

Objective. Fibrodysplasia ossificans progressiva (FOP) is a rare genetic condition in which progressive ossification of fibrous tissue, tendons and ligaments leads to severe physical handicap. Most affected individuals who have been studied have a recurrent 617G>A mutation in the ACVR1/ALK2 gene that codes for activin A type 1 receptor/activin-like kinase 2. The majority of publications on the genetics of FOP have concerned whites or Asians, and no genetic information is available concerning sub-Saharan blacks. The aim of the project was to determine whether or not this mutation is present in affected persons in South Africa.
Method. Molecular mutational analysis was undertaken on genomic DNA from peripheral blood leukocytes from 6 affected South African of different population groups (4 Xhosa, 1 coloured, 1 white).
Results. The 6 persons with FOP were all heterozygous for the ACVR1/ALK2 617G>A mutation. This mutation was absent in 6 controls.
Conclusion. Confirmation of the presence of this recurrent mutation facilitates diagnostic accuracy in affected persons in South Africa, and allows researchers to narrow the search for molecular targets for rational intervention to the ACVR1/ALK2 domain.