title: Molecular study of the 5 alpha-reductase type 2 gene in three European families with 5 alpha-reductase deficiency.
abstract: The molecular basis of 5 alpha-reductase (5 alpha R) deficiency was investigated in four patients from three European families. In the French family, the first patient was raised as a female, and gonadectomy was performed before puberty. The second sibling, also raised as female, differed in that gonadal removal was performed after the onset of pubertal masculinization. The other two patients, both from Polish families, developed masculinization of external genitalia during puberty. All patients developed a female sexual identity. In all cases, no known consanguinity or family history of 5 alpha R deficiency was reported. The genomic DNAs of the patients were sequenced after polymerase chain reaction amplification of the five exons of the 5 alpha R type 2 gene. We found two homozygous mutations responsible for glutamine to arginine and histidine to arginine substitution in families 1 and 3, respectively. In family 2, we found a heterozygous mutation responsible for an asparagine to serine substitution at position 193. The glutamine/arginine 126 mutation in the French family was previously reported in a Creole ethnic group, and the Polish histidine/arginine 231 mutation was previously reported in a patient from Chicago. Moreover, all of the mutations created new restriction sites, which were used to determine the kindred carrier status in the three families. Because 5 alpha R deficiency is known to be a heterogenous disease in terms of clinical and biochemical expression, our data suggest that molecular biology analysis of the type 2 gene could be an essential step in diagnosing 5 alpha R deficiency.
authors.affiliation: Centre de Recherches de l'Institut National de la Santé et de la Recherche Médicale, INSERM, Montpellier, France.
authors.forename: C
authors.initials: C
authors.lastname: Boudon
authors.forename: S
authors.initials: S
authors.lastname: Lumbroso
authors.forename: J M
authors.initials: JM
authors.lastname: Lobaccaro
authors.forename: M
authors.initials: M
authors.lastname: Szarras-Czapnik
authors.forename: T E
authors.initials: TE
authors.lastname: Romer
authors.forename: P
authors.initials: P
authors.lastname: Garandeau
authors.forename: P
authors.initials: P
authors.lastname: Montoya
authors.forename: C
authors.initials: C
authors.lastname: Sultan
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency* / Q000235:genetics*; D000293:Adolescent; D000595:Amino Acid Sequence; D001120:Arginine; D001216:Asparagine; D001483:Base Sequence; D012734:Disorders of Sex Development / Q000201:enzymology / Q000235:genetics*; D005091:Exons; D005260:Female; D005602:France; D005973:Glutamine; D006639:Histidine; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D017354:Point Mutation; D011044:Poland / Q000208:ethnology; D012694:Serine
chemical_list: D005973:Glutamine; D012694:Serine; D006639:Histidine; D001216:Asparagine; D001120:Arginine; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase