MUTATIONS OF THE 5-ALPHA-REDUCTASE TYPE-2 GENE IN 8 MEXICAN PATIENTS FROM 6 DIFFERENT PEDIGREES WITH 5-ALPHA-REDUCTASE-2 DEFICIENCY

BACKGROUND AND OBJECTIVE Male pseudohermaphroditism due to 5 alpha-red uctase deficiency was originally described in 1974. Recently, 5 alpha- reductase Type 2 gene defects have been found generally to be due to p oint 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 alph a-reductase deficiency were sampled in order to perform molecular stud ies. PATIENTS Eight 5 alpha-reductase deficient individuals from 6 unr elated families. MEASUREMENTS Single-strand conformational polymorphis m and DNA sequencing were performed after polymerase chain reaction am plification of each of the 5 exons of the gene. RESULTS Five different missense mutations were found, In 4 patients a cytosine to guanine su bstitution was observed at codon 212 in exon 4. Two siblings presented a cytosine to adenine substitution at codon 207 in exon 4. Another pa tient exhibited a guanine to adenine substitution at codon 34 in exon 1, whilst one individual presented 2 mutations: a guanine to adenine s ubstitution at codon 115 in exon 2 and a guanine to adenine substituti on at codon 203 in exon 4 (previously undescribed mutation). CONCLUSIO NS The presence of the same mutation in 4 patients from 3 families ind icates the increased prevalence of this mutation in a particular ethni c group, suggesting a common ancestry for the gene defect in these pat ients. The existence of hot spots is supported by the mutations in cod ons 34 and 207 which have also been found in other ethnic groups. Inte restingly, the patient who presented 2 different mutations, one of the m previously undescribed, was reared as a male and exhibited a more ma sculine phenotype. Further studies in patients with this and other mut ations will be needed to verify genotype-phenotype correlation.