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
| Autor: | Gil Guerra, Celso Eduardo Benedetti, Andréa Trevas Maciel-Guerra, Juliana Godoy Assumpção, Marcia Ribeiro Scolfaro, M. P. De Mello, M T M Baptista |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Sex Differentiation Blotting Western Mutation Missense Gonadal dysgenesis Biology Y chromosome medicine.disease_cause Gonadal Dysgenesis Polymerase Chain Reaction XY gonadal dysgenesis Open Reading Frames Drug Discovery medicine Escherichia coli Missense mutation Humans Genes sry Phosphorylation Transversion Codon Genetics (clinical) Genetics Mutation DNA Sex Determination Processes medicine.disease Molecular biology Pedigree Testis determining factor Phenotype HMG-Box Domains Molecular Medicine Female Male sex differentiation Protein Binding |
| Zdroj: | Journal of molecular medicine (Berlin, Germany). 80(12) |
| ISSN: | 0946-2716 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink