Uniparental disomy in steroid 5 alpha-reductase 2 deficiency

Steroid 5 alpha-reductase 2 deficiency is an autosomal recessive form of ma le pseudohermaphroditism caused by mutations in the SRD5A2 gene. In this st udy, we performed DNA analyses in two unrelated subjects bearing the enzyme deficiency and found differences in the mode of transmission for the disea se. The data showed that in both families the fathers were carriers for an E197D mutation, whereas the mothers were carriers for a P212R mutation. Pat ient 1 was identified as compound heterozygote because he had both alterati ons (E197D/P212R). On the contrary, patient 2 was found to be homozygous, b ut only for the paternal mutation. Because this finding could not be explai ned on the basis of nonpaternity or a chromosomal abnormality, the presence of uniparental disomy was suggested. The reduction to homozygosity for the E197D mutation, as confirmed by restriction analysis, supported this view. The results of our study give evidence of the first case of 5 alpha-reduct ase deficiency resulting from uniparental disomy and also disclose an alter nate mechanism whereby this enzymatic disorder can derive from a single par ent.