Mutations of SRY are the cause of 46,XY complete pure gonadal dysgenesis (PGD) in 10-15% of patients. In this study, DNA was isolated and sequenced from blood leukocytes and from paraffin-embedded gonadal tissue in five patients with 46,XY complete PGD. DNA binding capability was analyzed by three different methods. The structure of the full length SRY and its mutant proteins was carried out using a protein molecular model. DNA analysis revealed two mutations and one synonymous polymorphism: in patient #4 a Y96C mutation, and a E156 polymorphism; in patient #5 a S143G mosaic mutation limited to gonadal tissue. We demonstrated, by all methods used, that both mutant proteins reduced SRY DNA binding activity. The three-dimensional structure of SRY suggested that besides the HMG box, the carboxy-terminal region of SRY interacts with DNA. In conclusion, we identified two SRY mutations and a polymorphism in two patients with 46,XY complete PGD, demonstrating the importance of the carboxy-terminal region of SRY in DNA binding activity.
Bibliographical noteFunding Information:
Irene Sánchez was supported by a Consejo Nacional de Ciencia y Tecnología (CONACYT), by the Coordinación de Investigación en Salud, Instituto Mexicano del Seguro Social, and by a Dirección General de Estudios de Posgrado (DGEP), UNAM, fellowship award. Patricia Munguía was supported by Sistema Nacional de Investigadores del CONACYT fellowship award.
This work was supported by the Consejo Nacional de Ciencia y Tecnología (CONACYT), México; Grant: G29790M and by Coordinación de Investigación en Salud, Instituto Mexicano del Seguro Social, México, Grant: IMSS-2003/019.
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All Science Journal Classification (ASJC) codes
- Molecular Biology