Identification of mutations in the SRD5A2 gene in Thai patients with male pseudohermaphroditism

Objective

To describe two unrelated Thai patients with suspected 5α-reductase type 2 deficiency and perform mutation analysis of the SRD5A2 gene.

Design

Case report.

Setting

A pediatric endocrinology clinic at a university hospital.

Patient(s)

Two unrelated patients with 46,XY karyotype, born with ambiguous genitalia, were studied. One was reared as a boy and the other was reared as a girl.

Intervention(s)

The entire coding regions of the SRD5A2 gene were assessed by polymerase chain reaction (PCR) and sequencing analysis.

Main Outcome Measure(s)

Molecular characterization of the SRD5A2 gene.

Result(s)

Four different pathogenic mutations (three missense and one nonsense) were identified. These were located at exon 1 (p.Q6X and p.L20P), exon 3 (p.G183S), and exon 4 (p.G203S). The T>C transition (c.59T>C) resulting in a leucine-to-proline substitution at codon 20 (p.L20P) has not been previously described and was not detected in 100 unaffected, ethnic-matched control chromosomes. In addition, p.G183S, previously identified only among patients from mixed African–European ancestry and in the Dominican Republic, was also detected in a Thai patient.

Conclusion(s)

This study demonstrates that the SRD5A2 gene is responsible for 5α-reductase type 2 deficiency across different populations and emphasizes the important role of genetic testing for the definite diagnosis and genetic counseling before gender assignment or any surgical intervention.

Key Words: SRD5A2, 5α-reductase type 2 deficiency, ambiguous genitalia, novel mutation