New mutations, hotspots, and founder effects in Brazilian patients with steroid 5α-reductase deficiency type 2

摘要: Mutations of the steroid 5α-reductase type 2 (SRD5A2) gene in 46,XY subjects cause masculinization defects varying degrees, due to reduced or impaired enzymatic activity. In this study, sequence abnormalities SRD5A2 were assessed by polymerase chain reaction with specific primers and automated sequencing analysis DNA samples from 20 patients suspected deficiency 18 Brazilian families. Eleven presented homozygous single-base mutations (two first cousins four unrelated G183S, two R246W, one del642T, G196S, 217_218insC plus A49T variant heterozygosis), whereas compound heterozygotes (one Q126R/IVS3+1G>A, Q126R/del418T, brothers Q126R/G158R). Three heterozygous for A207D, R266W substitutions. The V89L polymorphism was found heterozygosis them (with A207D) case an otherwise normal sequence. also detected second without other abnormalities. Four harbor yet non-described mutations: a single nucleotide deletion (del642T), G158R amino acid substitution, splice junction mutation (IVS3+1G>A), insertion cytosine (217_218insC) occurring at CCCC motif. This is report single-nucleotide coding gene. addition these new mutations, investigation reveals prevalence G183S substitution among subset African–Brazilian presents evidences recurrence already known mutations.