title: SRD5A2 gene mutations and polymorphisms in Spanish 46,XY patients with a disorder of sex differentiation.
abstract: One hundred and forty-six index patients with 46,XY DSD in whom gonads were confirmed as testes were consecutively studied for a molecular diagnosis during the period 2002-2010. AR gene was analysed in all patients as the first candidate gene, yielding a mutation in 42.5% of cases and SRD5A2 gene was analysed as the second candidate gene, resulting in the characterization of 10 different mutations (p.Y91D, p.G115D, p.Q126R, p.R171S, p.Y188CfsX9, p.N193S, p.A207D, p.F219SfsX60, p.R227Q and p.R246W) in nine index patients (6.2% of the total number of 46,XY DSD patients). One of the mutations (p.Y188CfsX9) has never been reported. In addition, we genotyped SRD5A2 gene p.V89L and c.281+15T>C polymorphisms in 46,XY DSD and in 156 normal adult males and found that patients with SRD5A2 mutations or without a known molecular diagnosis presented a higher frequency of homozygous p.L89, homozygous TT and combined CCTT genotypes compared with controls. This result suggests that 46,XY DSD patient phenotypes may be influenced by SRD5A2 polymorphism genotypes. SRD5A2 gene mutations may not be as infrequent as previously considered in 46,XY DSD patients with variable degrees of external genitalia virilization at birth and normal T production and appears to be the second aetiology in our series.
authors.affiliation: Unidad Investigación Endocrinología y Nutrición Pediátricas, Institut de Recerca, Hospital Vall d'Hebron, CIBERER (Centro de Investigación Biomédica en Red), Instituto de Salud Carlos III, Universitat Autònoma de Barcelona, Barcelona, Spain. mfernand@ir.vhebron.net
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Cancio
authors.forename: L
authors.initials: L
authors.lastname: Audí
authors.forename: P
authors.initials: P
authors.lastname: Andaluz
authors.forename: N
authors.initials: N
authors.lastname: Torán
authors.forename: C
authors.initials: C
authors.lastname: Piró
authors.forename: M
authors.initials: M
authors.lastname: Albisu
authors.forename: M
authors.initials: M
authors.lastname: Gussinyé
authors.forename: D
authors.initials: D
authors.lastname: Yeste
authors.forename: M
authors.initials: M
authors.lastname: Clemente
authors.forename: J
authors.initials: J
authors.lastname: Martínez-Mora
authors.forename: A
authors.initials: A
authors.lastname: Blanco
authors.forename: M L
authors.initials: ML
authors.lastname: Granada
authors.forename: M
authors.initials: M
authors.lastname: Marco
authors.forename: J
authors.initials: J
authors.lastname: Ferragut
authors.forename: J P
authors.initials: JP
authors.lastname: López-Siguero
authors.forename: M
authors.initials: M
authors.lastname: Beneyto
authors.forename: C
authors.initials: C
authors.lastname: Carles
authors.forename: A
authors.initials: A
authors.lastname: Carrascosa
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D012734:Disorders of Sex Development / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D013030:Spain
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human