title: Compound heterozygous mutations in the SRD5A2 gene exon 4 in a male pseudohermaphrodite patient of Chinese origin.
abstract: The goal of this study was to perform 5-alpha-reductase type 2 gene (SRD5A2) analysis in a male pseudohermaphrodite (MPH) patient with normal testosterone (T) production and normal androgen receptor (AR) gene coding sequences. A patient of Chinese origin with ambiguous genitalia at 14 months, a 46,XY karyotype, and normal T secretion under human chorionic gonadotropin (hCG) stimulation underwent a gonadectomy at 20 months. Exons 1-8 of the AR gene and exons 1-5 of the SRD5A2 gene were sequenced from peripheral blood DNA. AR gene coding sequences were normal. SRD5A2 gene analysis revealed 2 consecutive mutations in exon 4, each located in a different allele: 1) a T nucleotide deletion, which predicts a frameshift mutation from codon 219, and 2) a missense mutation at codon 227, where the substitution of guanine (CGA) by adenine (CAA) predicts a glutamine replacement of arginine (R227Q). Testes located in the inguinal canal showed a normal morphology for age. The patient was a compound heterozygote for SRD5A2 mutations, carrying 2 mutations in exon 4. The patient showed an R227Q mutation that has been described in an Asian population and MPH patients, along with a novel frameshift mutation, Tdel219. Testis morphology showed that, during early infancy, the 5-alpha-reductase enzyme deficiency may not have affected interstitial or tubular development.
authors.affiliation: Unidad Investigación Endocrinología y Nutrición Pediátricas, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Fernández-Cancio
authors.forename: Manuel
authors.initials: M
authors.lastname: Nistal
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gracia
authors.forename: M Antonia
authors.initials: MA
authors.lastname: Molina
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Tovar
authors.forename: Cristina
authors.initials: C
authors.lastname: Esteban
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrascosa
authors.forename: Laura
authors.initials: L
authors.lastname: Audí
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000225:Adenine; D001120:Arginine; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D012734:Disorders of Sex Development / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016368:Frameshift Mutation; D017353:Gene Deletion; D006147:Guanine; D006579:Heterozygote; D006728:Hormones / Q000097:blood; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D013737:Testis / Q000473:pathology
chemical_list: D006728:Hormones; D006147:Guanine; D001120:Arginine; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D000225:Adenine