Fumarase deficiency caused by homozygous P131R mutation and paternal partial isodisomy of chromosome 1

Abstract

We report on the first case of fumarase deficiency (FD) caused by uniparental isodisomy. An affected patient was found to be homozygous for the P131R mutation in the FH gene. In this nonconsanguineous family, the unaffected father was found to be heterozygous for the same mutation, and the mother was found to be homozygous wild‐type. Analysis of chromosome 1 markers showed that the patient inherited both paternal alleles with complete absence of the maternal homolog. The two copies of the paternal chromosome 1 are heterodisomic for most of the chromosome except the distal 1q region which is isodisomic for the mutant alleles of the FH gene. The genotypes of other chromosome markers are consistent with the patient inheriting alleles from both parents. Although FD is an autosomal recessive disorder, the effects of uniparental disomy (UPD) should be considered in genetic counseling since the recurrence risk of an affected child is significantly reduced when the disorder is due to UPD.