| Full text | |
| Author(s): |
Cunha, J. L.
[1]
;
Soardi, F. C.
[1]
;
Bernardi, R. D.
[1]
;
Oliveira, L. E. C.
[1]
;
Benedetti, C. E.
[2]
;
Guerra-Junior, G.
[3, 4]
;
Maciel-Guerra, A. T.
[5, 4]
;
de Mello, M. P.
[1, 4]
Total Authors: 8
|
| Affiliation: | [1] Univ Estadual Campinas, Ctr Biol Mol & Engn Genet, Campinas, SP - Brazil
[2] Ctr Nacl Pesquisa Energia & Mat, Lab Nacl Biociencias, Campinas, SP - Brazil
[3] Univ Estadual Campinas, Fac Ciencias Med, Dept Pediat, Campinas, SP - Brazil
[4] Univ Estadual Campinas, Fac Ciencias Med, Grp Interdisciplinar Estudos Determinacao & Difer, Campinas, SP - Brazil
[5] Univ Estadual Campinas, Fac Ciencias Med, Dept Med Genet, Campinas, SP - Brazil
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | Brazilian Journal of Medical and Biological Research; v. 44, n. 4, p. 361-365, APR 2011. |
| Web of Science Citations: | 6 |
| Abstract | |
Male sex determination in humans is controlled by the SRY gene, which encodes a transcriptional regulator containing a conserved high mobility group box domain (HMG-box) required for DNA binding. Mutations in the SRY HMG-box affect protein function, causing sex reversal phenotypes. In the present study, we describe a 19-year-old female presenting 46,XY karyotype with hypogonadism and primary amenorrhea that led to the diagnosis of 46, XY complete gonadal dysgenesis. The novel p.E89K missense mutation in the SRY HMG-box was identified as a de novo mutation. Electrophoretic mobility shift assays showed that p.E89K almost completely abolished SRY DNA-binding activity, suggesting that it is the cause of SRY function impairment. In addition, we report the occurrence of the p.G95R mutation in a 46, XY female with complete gonadal dysgenesis. According to the three-dimensional structure of the human SRY HMG-box, the substitution of the conserved glutamic acid residue by the basic lysine at position 89 introduces an extra positive charge adjacent to and between the positively charged residues R86 and K92, important for stabilizing the HMG-box helix 2 with DNA. Thus, we propose that an electrostatic repulsion caused by the proximity of these positive charges could destabilize the tip of helix 2, abrogating DNA interaction. (AU) | |
| FAPESP's process: | 08/03168-1 - Analysis of SRY gene regulation by SP1 and WT1 proteins |
| Grantee: | Fernanda Caroline Soardi |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 07/00900-0 - Mutation analysis and effects on the SRY gene expression in XY gonadal dysgenesis |
| Grantee: | José Luiz Rosenberis Cunha Júnior |
| Support Opportunities: | Scholarships in Brazil - Master |