title: Novel mutations affecting SRY DNA-binding activity: the HMG box N65H associated with 46,XY pure gonadal dysgenesis and the familial non-HMG box R30I associated with variable phenotypes.
abstract: The SRY gene (sex-determining region of the Y chromosome) initiates the process of male sex differentiation in mammalians. In humans mutations in the SRY gene have been reported to account for 10-15% of the XY sex reversal cases. We describe here two novel missense mutations in the SRY gene after the screening of 17 patients, including 3 siblings, with 46,XY gonadal dysgenesis and 4 true hermaphrodites. One of the mutations, an A to C transversion within the HMG box, causes the N65H substitution and it was found in a patient presenting 46,XY pure gonadal dysgenesis. The Escherichia coli expressed SRY(N65H) protein did not present DNA-binding activity in vitro. The other mutation, a G to T transversion, causes the R30I substitution. This mutation was found in affected and nonaffected members of a family, including the father, two siblings with partial gonadal dysgenesis, a phenotypic female with pure gonadal dysgenesis, and three nonaffected male siblings. The G to T base change was not found in the SRY sequence of 100 normal males screened by ASO-PCR. The R30I mutation is located upstream to the HMG box, within the (29)RRSSS(33) phosphorylation site. The E. coli expressed SRY(R30I) protein was poorly phosphorylated and consequently showed reduced DNA-binding capacity in vitro.
authors.affiliation: Centro de Biologia Molecular e Engenharia Genética, Universidade Estadual de Campinas, 13083-970 Campinas, SP, Brazil.
authors.forename: J G
authors.initials: JG
authors.lastname: Assumpção
authors.forename: C E
authors.initials: CE
authors.lastname: Benedetti
authors.forename: A T
authors.initials: AT
authors.lastname: Maciel-Guerra
authors.forename: G
authors.initials: G
authors.lastname: Guerra
authors.forename: M T M
authors.initials: MT
authors.lastname: Baptista
authors.forename: M R
authors.initials: MR
authors.lastname: Scolfaro
authors.forename: M P
authors.initials: MP
authors.lastname: de Mello
mesh_terms: D015153:Blotting, Western; D003062:Codon; D004247:DNA / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D024282:Genes, sry; D006059:Gonadal Dysgenesis / Q000235:genetics*; D024742:HMG-Box Domains; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D016366:Open Reading Frames; D010375:Pedigree; D010641:Phenotype; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D019849:Sex Determination Processes; D012733:Sex Differentiation
chemical_list: D003062:Codon; D004247:DNA