biostudies-literatureSirokha DSimons FoundationSwiss National Science FoundationNational Academy of Sciences of Ukraine11575https://www.ebi.ac.uk/biostudies/studies/S-EPMC12692329biostudies-literatureUnknown26(23)46,XY gonadal dysgenesis, characterised by absent or defective testicular development in individuals with a 46,XY karyotype, results from disruptions in the genetic programme governing testis determination and differentiation during embryogenesis. While monogenic causes explain approximately 50% of cases, emerging evidence suggests an oligogenic basis in some patients. However, many cases remain without a definitive molecular diagnosis. In this study, we investigated a patient with 46,XY gonadal dysgenesis to explore the underlying genetic aetiology. Whole-exome sequencing in the patient did not reveal any pathogenic variants in genes previously associated with this condition. Instead, it detected rare variants in <i>STARD9</i> and <i>CDK5RAP2</i>, which encode centrosomal proteins known tInternational journal of molecular sciencesSTARD9 and CDK5RAP2-Novel Candidate Genes for 46,XY Complete Gonadal Dysgenesis.PMC12692329SCOPES IZ73Z0_152347/112905891523470121U110054Kusz-Zamelczyk KGorodna OMayere CSamson OSirokha DLemanska ZLivshits LKhalangot MKwiatkowska KKalynovskyi VNef SRayevsky AKunik AfalseSTARD9 and CDK5RAP2-Novel Candidate Genes for 46,XY Complete Gonadal Dysgenesis.46,XY gonadal dysgenesis, characterised by absent or defective testicular development in individuals with a 46,XY karyotype, results from disruptions in the genetic programme governing testis determination and differentiation during embryogenesis. While monogenic causes explain approximately 50% of cases, emerging evidence suggests an oligogenic basis in some patients. However, many cases remain without a definitive molecular diagnosis. In this study, we investigated a patient with 46,XY gonadal dysgenesis to explore the underlying genetic aetiology. Whole-exome sequencing in the patient did not reveal any pathogenic variants in genes previously associated with this condition. Instead, it detected rare variants in <i>STARD9</i> and <i>CDK5RAP2</i>, which encode centrosomal proteins known t2025-01-01T00:00:00Z2025 Nov2026-05-26T20:02:49.989Z2026-05-24T03:12:19.442ZS-EPMC126923294137372610.3390/ijms262311575