A novel frameshift mutation in the 5alpha-reductase type 2 gene in Korean sisters with male pseudohermaphroditism

To describe two cases of 5alpha-reductase deficiency and the identification of a novel frameshift mutation in this sibling pair.

Case report.

An adolescent clinic at a university hospital.

A 14-year-old girl and her younger sister, who presented with primary amenorrhea, deepening of the voice, and clitoromegaly.

Deoxyribonucleic acid was extracted from peripheral blood, and 8 exons of the androgen receptor gene and 5 exons of the steroid 5alpha-reductase type 2 gene (encoded by SRD5A2 gene) were amplified by polymerase chain reaction and subjected to sequence analyses.

Genetic diagnosis of 5alpha-reductase deficiency.

There was no evidence of a genetic abnormality in the 8 screened exons of the androgen receptor gene, but exon 4 of the SRD5A2 gene showed a novel homozygous deletion of the thymine at nucleotide position c.655 (c.655delT), leading to a frameshift mutation predicted to result in an abnormally long protein with an extended termination signal.

The molecular characterization of the mutation can be a relevant tool for a correct diagnosis of 5alpha-reductase deficiency.