title: Molecular analysis of the SRD5A2 in 46,XY subjects with incomplete virilization: the P212R substitution of the steroid 5alpha-reductase 2 may constitute an ancestral founder mutation in Mexican patients.
abstract: Inactivating mutations of the SRD5A2 gene result in steroid 5α-reductase 2 deficiency, an autosomal recessive disorder expressed as a male-limited disorder of sex development. Herein, genomic DNA was isolated from 11 new patients with apparent steroid 5α-reductase 2 deficiency. Coding sequence abnormalities in SRD5A2 were assessed by exon-specific polymerase chain reaction, single-stranded conformation polymorphism, and direct sequencing. Likewise, enzymatic activity of the P212R gene variant of SRD5A2 was assessed. DNA analysis revealed mutations in all patients (G115D, R171S, N193S, E197D, G203S, P212R). Three individuals were compound heterozygotes, 6 were homozygotes, and 2 more were single heterozygotes for SRD5A2 mutations; remarkably, 40% of the mutant alleles (9/22) contained the gene variant P212R. The results described in this study represent, along with our previous reports, the largest number of patients with steroid 5α-reductase 2 deficiency belonging to nonrelated families. Regarding the frequency of the p.P212R mutation in our population and its presence throughout all of our country, it allows us to hypothesize that the presence of this mutation may constitute a founder gene effect.
authors.affiliation: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D.F., México.
authors.forename: Felipe
authors.initials: F
authors.lastname: Vilchis
authors.forename: Luis
authors.initials: L
authors.lastname: Ramos
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Méndez
authors.forename: Socorro
authors.initials: S
authors.lastname: Benavides
authors.forename: Patricia
authors.initials: P
authors.lastname: Canto
authors.forename: Bertha
authors.initials: B
authors.lastname: Chávez
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency / Q000235:genetics*; D000293:Adolescent; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D058490:Disorder of Sex Development, 46,XY / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D008800:Mexico / Q000453:epidemiology; D009154:Mutation
chemical_list: D008565:Membrane Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human