Mutation Analysis and Prenatal Exclusion of Fibrodysplasia Ossificans Progressiva in a Chinese Fetus.

Aims: Fibrodysplasia ossificans progressiva (FOP) is a rare and severely disabling autosomal dominant disorder characterized by congenital malformations of the great toes and progressive postnatal heterotopic ossification. A point mutation in the activin receptor IA (ACVR1) gene is the cause of FOP. Most of the reported cases of FOP are sporadic and caused by de novo mutations; however, some rare cases can also result from parental germline mosaicism associated with a greater risk of recurrence in successive pregnancies. Therefore, once the pathogenic mutation has been identified in the proband, it is relative cheaper and important to perform prenatal diagnostic tests to exclude the recurrence risk of FOP in subsequent pregnancies. In this study, we first investigated the mutation in the ACVR1 gene in a Chinese FOP patient and then performed prenatal tests to exclude the risk of recurrence in the patient's unborn sibling.
Methods: A couple visited our clinic with their 4-year-old son, who was clinically diagnosed with FOP, for genetic counseling. Genetic testing was performed by amplifying all the nine exons of the ACVR1 gene using the conventional polymerase chain reaction. Further, DNA sequencing was used to determine the mutation based on the results of a mutation screening using denaturing high-performance liquid chromatography. Subsequently, a prenatal test was performed using the same technique as that used for the proband.
Results: A recurrent single nucleotide mutation c.617 G>A (R206H) of the ACVR1 gene was identified in the patient; however, both the parents had a normal ACVR1 gene. Prenatal tests showed that the fetus did not carry the pathogenic mutation.
Conclusion: The results confirmed that a recurrent single nucleotide mutation c.617 G>A (R206H) was the genetic cause of FOP and explored the utility of prenatal testing in excluding the risk of recurrence in the successive pregnancy.