DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis

Irene Sánchez-Moreno, Patricia Canto, Patricia Munguía, Mario Bermúdez de León, Bulmaro Cisneros, Felipe Vilchis, Edgardo Reyes, Juan Pablo Méndez

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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. © 2008 Elsevier Ireland Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)212-218
Number of pages7
JournalMolecular and Cellular Endocrinology
DOIs
Publication statusPublished - 27 Feb 2009
Externally publishedYes

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46,XY Gonadal Dysgenesis
DNA
Polymorphism
Mutation
Mutant Proteins
Tissue
Molecular Models
Ireland
Paraffin
Leukocytes
Blood

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Sánchez-Moreno, Irene ; Canto, Patricia ; Munguía, Patricia ; de León, Mario Bermúdez ; Cisneros, Bulmaro ; Vilchis, Felipe ; Reyes, Edgardo ; Méndez, Juan Pablo. / DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis. In: Molecular and Cellular Endocrinology. 2009 ; pp. 212-218.
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DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis. / Sánchez-Moreno, Irene; Canto, Patricia; Munguía, Patricia; de León, Mario Bermúdez; Cisneros, Bulmaro; Vilchis, Felipe; Reyes, Edgardo; Méndez, Juan Pablo.

In: Molecular and Cellular Endocrinology, 27.02.2009, p. 212-218.

Research output: Contribution to journalArticle

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T1 - DNA binding activity studies and computational approach of mutant SRY in patients with 46, XY complete pure gonadal dysgenesis

AU - Sánchez-Moreno, Irene

AU - Canto, Patricia

AU - Munguía, Patricia

AU - de León, Mario Bermúdez

AU - Cisneros, Bulmaro

AU - Vilchis, Felipe

AU - Reyes, Edgardo

AU - Méndez, Juan Pablo

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AB - 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. © 2008 Elsevier Ireland Ltd. All rights reserved.

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