title: Ambiguous external genitalia due to defect of 5-α-reductase in seven Iraqi patients: prevalence of a novel mutation.
abstract: We report on seven Iraqi patients with 46,XY karyotype and ambiguous genitalia characterized by perineo-scrotal hypospadias, bifid scrotum, clitoris like phallus, palpable testes in inguinal canal and pseudovagina. Patients were raised five as females and two as males. They are all unrelated with the exception of two couples of brothers. The diagnosis of 5-α-reductase-2 deficiency syndrome was first hypothesized on clinical grounds and then confirmed by molecular analysis. Direct sequencing analysis of the SRD5A2 gene revealed in five patients a novel homozygous frame-shift mutation (c.453delC) and in two related patients a previous reported missense mutation. The presence of the same mutation in unrelated patients of the same population suggests a possible founder effect. This report brings the 5-α-reductase-2 deficiency syndrome to the attention of clinical geneticists and child surgeons and discusses the appropriate clinical and surgical strategies for treating these patients.
authors.affiliation: Medical Genetics, University of Siena, Siena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Marco
authors.forename: Anna Lavinia
authors.initials: AL
authors.lastname: Bulotta
authors.forename: Concetta
authors.initials: C
authors.lastname: Varetti
authors.forename: Laura
authors.initials: L
authors.lastname: Dosa
authors.forename: Angela
authors.initials: A
authors.lastname: Michelucci
authors.forename: Fulvia
authors.initials: F
authors.lastname: Baldinotti
authors.forename: Daniela
authors.initials: D
authors.lastname: Meucci
authors.forename: Cinzia
authors.initials: C
authors.lastname: Castagnini
authors.forename: Caterina
authors.initials: C
authors.lastname: Lo Rizzo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Maggio
authors.forename: Paolo
authors.initials: P
authors.lastname: Simi
authors.forename: Francesca
authors.initials: F
authors.lastname: Mari
authors.forename: Silvano
authors.initials: S
authors.lastname: Bertelloni
authors.forename: Alessandra
authors.initials: A
authors.lastname: Renieri
authors.forename: Mario
authors.initials: M
authors.lastname: Messina
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D042944:Cholestenone 5 alpha-Reductase / Q000172:deficiency* / Q000235:genetics; D003241:Consanguinity; D012734:Disorders of Sex Development / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D005260:Female; D006801:Humans; D007493:Iraq; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D059645:Mutation Rate; D010375:Pedigree; D010641:Phenotype
chemical_list: D008565:Membrane Proteins; D042944:Cholestenone 5 alpha-Reductase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human
keywords: 46,XY DSD; 5-α-reductase type 2; AR; DHT; DSD; Founder effect; MRI; Phenotypic variability; SRD; SRD5A2; SRD5A2 gene; Steroid 5-α-reductase-2 deficiency; T; androgen receptor; dihydrotestosterone; hCG; human chorionic gonadotropin; magnetic resonance imaging; sex development disorder; steroid 5-α-reductase deficiency; testosterone