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.
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Authors | J G Assumpção, C E Benedetti, A T Maciel-Guerra, G Guerra Jr, M T M Baptista, M R Scolfaro, M P de Mello |
Journal | Journal of molecular medicine (Berlin, Germany)
(J Mol Med (Berl))
Vol. 80
Issue 12
Pg. 782-90
(Dec 2002)
ISSN: 0946-2716 [Print] Germany |
PMID | 12483463
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Blotting, Western
- Codon
- DNA
(metabolism)
- Escherichia coli
(metabolism)
- Female
- Genes, sry
- Gonadal Dysgenesis
(genetics)
- HMG-Box Domains
- Humans
- Male
- Mutation
- Mutation, Missense
- Open Reading Frames
- Pedigree
- Phenotype
- Phosphorylation
- Polymerase Chain Reaction
- Protein Binding
- Sex Determination Processes
- Sex Differentiation
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