Disorders of Sex Development in a Large Ukrainian Cohort: Clinical Diversity and Genetic Findings
| Autor: | Evgenia, Globa, Natalia, Zelinska, Yulia, Shcherbak, Joelle, Bignon-Topalovic, Anu, Bashamboo, Ken, MсElreavey |
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| Přispěvatelé: | Ministry of Health of Ukraine, Génétique du Développement humain - Human developmental genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work is funded in part by a research grant from the European Society of Pediatric Endocrinology, and by the Agence Nationale de la Recherche (ANR), ANR-10-LABX-73 REVIVE, ANR-17-CE14-0038-01, ANR-19-CE14-0022 and ANR-19-CE14-0012 and by the Ministry of Health of Ukraine (0117U003036)., 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-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) |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Male
MESH: Mutation 46 XX Disorders of Sex Development MESH: Sexual Development phenotype Endocrinology Diabetes and Metabolism [SDV]Life Sciences [q-bio] Sex Chromosome Disorders of Sex Development Disorders of Sex Development MESH: Sex Chromosome Disorders of Sex Development XY and 46 MESH: Hypogonadism XX disorders of sex development Humans MESH: In Situ Hybridization Fluorescence genes In Situ Hybridization Fluorescence MESH: 46 XX Disorders of Sex Development MESH: Humans Hypogonadism Sexual Development MESH: Male karyotype whole exome sequencing (WES) Mutation Female MESH: Disorders of Sex Development MESH: Female |
| Zdroj: | Frontiers in Endocrinology Frontiers in Endocrinology, 2022, 13, pp.810782. ⟨10.3389/fendo.2022.810782⟩ |
| ISSN: | 1664-2392 |
| DOI: | 10.3389/fendo.2022.810782⟩ |
| Popis: | BackgroundThe clinical profile and genetics of individuals with Disorders/Differences of Sex Development (DSD) has not been reported in Ukraine.Materials and MethodsWe established the Ukrainian DSD Register and identified 682 DSD patients. This cohort includes, 357 patients (52.3% [303 patients with Turner syndrome)] with sex chromosome DSD, 119 (17.5%) with 46,XY DSD and 206 (30.2%) with 46,XX DSD. Patients with sex chromosome DSD and congenital adrenal hyperplasia (CAH, n=185) were excluded from further studies. Fluorescence in situ hybridization (FISH) was performed for eight 46,XX boys. 79 patients underwent Whole Exome Sequencing (WES).ResultsThe majority of patients with 46,XY and 46,XX DSD (n=140), were raised as female (56.3% and 61.9% respectively). WES (n=79) identified pathogenic (P) or likely pathogenic (LP) variants in 43% of the cohort. P/LP variants were identified in the androgen receptor (AR) and NR5A1 genes (20.2%). Variants in other DSD genes including AMHR2, HSD17B3, MYRF, ANOS1, FGFR11, WT1, DHX37, SRD5A1, GATA4, TBCE, CACNA1A and GLI2 were identified in 22.8% of cases. 83.3% of all P/LP variants are novel. 35.3% of patients with a genetic diagnosis had an atypical clinical presentation. A known pathogenic variant in WDR11, which was reported to cause congenital hypogonadotropic hypogonadism (CHH), was identified in individuals with primary hypogonadism.ConclusionsWES is a powerful tool to identify novel causal variants in patients with DSD, including a significant minority that have an atypical clinical presentation. Our data suggest that heterozygous variants in the WDR11 gene are unlikely to cause of CHH. |
| Databáze: | OpenAIRE |
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