Additional evidence for the role of chromosomal imbalances and SOX8, ZNRF3 and HHAT gene variants in early human testis development
| Autor: | Rjiba, Khouloud, Mougou-Zerelli, Soumaya, Hamida, Imen Hadj, Saad, Ghada, Khadija, Bochra, Jelloul, Afef, Slimani, Wafa, Hasni, Yosra, Dimassi, Sarra, Khelifa, Hela Ben, Sallem, Amira, Kammoun, Molka, Abdallah, Hamza Hadj, Gribaa, Moez, Bignon-Topalovic, Joelle, Chelly, Sami, Khairi, Hédi, Bibi, Mohamed, Kacem, Maha, Saad, Ali, Bashamboo, Anu, Mcelreavey, Kenneth |
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| Přispěvatelé: | Centre Hospitalo-Universitaire Farhat Hached, Université de Monastir - University of Monastir (UM), Université de Sousse, Génétique du Développement humain - Human developmental genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), CHU Fattouma Bourguiba [Monastir] (HFB), This work is funded in part by a research grant from the European Society of Pediatric Endocrinology, a scholarship from the Tunisian government, and by the Agence Nationale de la Recherche (ANR), ANR-10-LABX-73 REVIVE, ANR-17-CE14-0038–01, ANR-19-CE14-0022, ANR-20-CE14-0007 and ANR-19-CE14-0012., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), ANR-17-CE14-0038,MGonDev,Etude des mécanismes du développement des gonades chez l'homme(2017), ANR-19-CE14-0022,SexDiff,Régulation de la détermination du sexe et de la différenciation ovarienne : implications dans les troubles du développement sexuel(2019), ANR-20-CE14-0007,Goldilocks,Analyse intégrée du rôle du facteur de transcription SF-1 / NR5A1 et de ses gènes cibles dépendants du dosage dans la fonction gonadique et les troubles du développement sexuel (DSD)(2020), ANR-19-CE14-0012,RNA-SEX,Fonction de l'ARN hélicase dans la détermination du sexe chez les vertébrés et les troubles du développement du sexe chez l'homme (DSD)(2019) |
| Rok vydání: | 2023 |
| Předmět: |
Cytogenetic abnormalities
MESH: Humans MESH: Mutation MESH: Sexual Development MESH: Testis [SDV]Life Sciences [q-bio] MESH: Sex Differentiation XY DSD Obstetrics and Gynecology MESH: Gonadal Dysgenesis 46 XY MESH: Acyltransferases MESH: Phenotype MESH: SOXE Transcription Factors MESH: Ubiquitin-Protein Ligases MESH: Male MESH: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase Endocrinology Reproductive Medicine Disorders of sex development (DSD) MESH: Membrane Proteins Whole exome sequencing(WES) MESH: Female Developmental Biology |
| Zdroj: | Reproductive Biology and Endocrinology Reproductive Biology and Endocrinology, 2023, 21 (1), pp.2. ⟨10.1186/s12958-022-01045-7⟩ |
| ISSN: | 1477-7827 |
| DOI: | 10.1186/s12958-022-01045-7 |
| Popis: | Abstract 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. |
| Databáze: | OpenAIRE |
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