Additional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development.

Autor: Rjiba K; Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Human Reproduction, Farhat Hached University Teaching Hospital, Sousse, Tunisia.; Higher Institute of Biotechnology Monastir, University of Monastir, Monastir, Tunisia.; Unité de Services Communs en Génétique Humaine, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia.; Human Developmental Genetics Unit, CNRS UMR 3738, Institut Pasteur, Paris, France., Mougou-Zerelli S; Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Human Reproduction, Farhat Hached University Teaching Hospital, Sousse, Tunisia.; Unité de Services Communs en Génétique Humaine, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia., Hamida IH; Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Human Reproduction, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Saad G; Department of Endocrinology, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Khadija B; Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Human Reproduction, Farhat Hached University Teaching Hospital, Sousse, Tunisia.; Higher Institute of Biotechnology Monastir, University of Monastir, Monastir, Tunisia.; Unité de Services Communs en Génétique Humaine, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia., Jelloul A; Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Human Reproduction, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Slimani W; Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Human Reproduction, Farhat Hached University Teaching Hospital, Sousse, Tunisia.; Unité de Services Communs en Génétique Humaine, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia., Hasni Y; Department of Endocrinology, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Dimassi S; Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Human Reproduction, Farhat Hached University Teaching Hospital, Sousse, Tunisia.; Unité de Services Communs en Génétique Humaine, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia., Khelifa HB; Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Human Reproduction, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Sallem A; Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Human Reproduction, Farhat Hached University Teaching Hospital, Sousse, Tunisia.; Laboratory of Human Cytogenetics and Biology of Reproduction, Fattouma Bourguiba University Teaching Hospital, Monastir, Tunisia., Kammoun M; Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Human Reproduction, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Abdallah HH; Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Human Reproduction, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Gribaa M; Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Human Reproduction, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Bignon-Topalovic J; Human Developmental Genetics Unit, CNRS UMR 3738, Institut Pasteur, Paris, France., Chelly S; Private Gynecologist Sousse, Sousse, Tunisia., Khairi H; Department of Gynecology and Obstetrics, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Bibi M; Department of Gynecology and Obstetrics, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Kacem M; Department of Endocrinology, Farhat Hached University Teaching Hospital, Sousse, Tunisia., Saad A; Laboratory of Human Cytogenetics, Molecular Genetics and Biology of Human Reproduction, Farhat Hached University Teaching Hospital, Sousse, Tunisia.; Unité de Services Communs en Génétique Humaine, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia., Bashamboo A; Human Developmental Genetics Unit, CNRS UMR 3738, Institut Pasteur, Paris, France., McElreavey K; Human Developmental Genetics Unit, CNRS UMR 3738, Institut Pasteur, Paris, France. kenneth.mcelreavey@pasteur.fr.
Jazyk: angličtina
Zdroj: Reproductive biology and endocrinology : RB&E [Reprod Biol Endocrinol] 2023 Jan 11; Vol. 21 (1), pp. 2. Date of Electronic Publication: 2023 Jan 11.
DOI: 10.1186/s12958-022-01045-7
Abstrakt: Background: Forty-six ,XY Differences/Disorders of Sex Development (DSD) are characterized by a broad phenotypic spectrum ranging from typical female to male with undervirilized external genitalia, or more rarely testicular regression with a typical male phenotype. Despite progress in the genetic diagnosis of DSD, most 46,XY DSD cases remain idiopathic.
Methods: To determine the genetic causes of 46,XY DSD, we studied 165 patients of Tunisian ancestry, who presented a wide range of DSD phenotypes. Karyotyping, candidate gene sequencing, and whole-exome sequencing (WES) were performed.
Results: Cytogenetic abnormalities, including a high frequency of sex chromosomal anomalies (85.4%), explained the phenotype in 30.9% (51/165) of the cohort. Sanger sequencing of candidate genes identified a novel pathogenic variant in the SRY gene in a patient with 46,XY gonadal dysgenesis. An exome screen of a sub-group of 44 patients with 46,XY DSD revealed pathogenic or likely pathogenic variants in 38.6% (17/44) of patients.
Conclusion: Rare or novel pathogenic variants were identified in the AR, SRD5A2, ZNRF3, SOX8, SOX9 and HHAT genes. Overall our data indicate a genetic diagnosis rate of 41.2% (68/165) in the group of 46,XY DSD.
(© 2023. The Author(s).)
Databáze: MEDLINE
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