ABSTRACT
BACKGROUND AND OBJECTIVE: Male pseudohermaphroditism due to 5 alpha-reductase deficiency was originally described in 1974. Recently, 5 alpha-reductase Type 2 gene defects have been found generally to be due to point mutations within the 5 exons of the 5 alpha-reductase-2 gene. In this report, we describe the molecular study of patients with 5 alpha-reductase deficiency. DESIGN: Previously diagnosed patients with 5 alpha-reductase deficiency were sampled in order to perform molecular studies. PATIENTS: Eight 5 alpha-reductase deficient individuals from 6 unrelated families. MEASUREMENTS: Single-strand conformational polymorphism and DNA sequencing were performed after polymerase chain reaction amplification of each of the 5 exons of the gene. RESULTS: Five different missense mutations were found. In 4 patients a cytosine to guanine substitution was observed at codon 212 in exon 4. Two siblings presented a cytosine to adenine substitution at codon 207 in exon 4. Another patient exhibited a guanine to adenine substitution at codon 34 in exon 1, whilst one individual presented 2 mutations: a guanine to adenine substitution at codon 115 in exon 2 and a guanine to adenine substitution at codon 203 in exon 4 (previously undescribed mutation). CONCLUSIONS: The presence of the same mutation in 4 patients from 3 families indicates the increased prevalence of this mutation in a particular ethnic group, suggesting a common ancestry for the gene defect in these patients. The existence of hot spots is supported by the mutations in codons 34 and 207 which have also been found in other ethnic groups. Interestingly, the patient who presented 2 different mutations, one of them previously undescribed, was reared as a male and exhibited a more masculine phenotype. Further studies in patients with this and other mutations will be needed to verify genotype-phenotype correlation.