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. [Copyright &y& Elsevier]