• PMID: 31523625
• Gene Name: SOX3
• Condition: Hypospadias
• Association: Associated
• Mutation: SOX3 gene duplications in a 46,XX SRY-negative male
• Population size: 1
• Population details: 1
• Age: 11-year-old
• Sex: Male
• Infertility type: Male infertility

Duplication of The SOX3 Gene in an Sry-negative 46,XX Male with Associated Congenital Anomalies of Kidneys and the Urinary Tract: Case Report and Review of the Literature

Tasic V, Mitrotti A, Riepe FG, Kulle AE, Laban N, Polenakovic M, Plaseska-Karanfilska D, Sanna-Cherchi S, Kostovski M, Gucev Z.

Disorders of sex development (DSD) are a group of rare conditions characterized by discrepancy between chromosomal sex, gonads and external genitalia. Congenital abnormalities of the kidney and urinary tract are often associated with DSD, mostly in multiple malformation syndromes. We describe the case of an 11-year-old Caucasian boy, with right kidney hypoplasia and hypospadias. Genome-wide copy number variation (CNV) analysis revealed a unique duplication of about 550 kb on chromosome Xq27, and a 46,XX karyotype, consistent with a sex reversal phenotype. This region includes multiple genes, and, among these, SOX3 emerged as the main phenotypic driver. This is the fifth case reporting a genomic imbalance involving the SOX3 gene in a 46,XX SRY-negative male, and the first with associated renal malformations. Our data provide plausible links between SOX3 gene dosage and kidney malformations. It is noteworthy that the current and reported SOX3 gene duplications are below the detection threshold of standard karyotypes and were found only by analyzing CNVs using DNA microarrays. Therefore, all 46,XX SRY-negative males should be screened for SOX3 gene duplications with DNA microarrays. FAU - Tasic, V AU - Tasic V AD - Medical Faculty Skopje, Skopje, Republic of Macedonia. FAU - Mitrotti, A AU - Mitrotti A AD - Division of Nephrology, Columbia University, New York, NY, USA. FAU - Riepe, F G AU - Riepe FG AD - Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University Hospital Schleswig-Holstein, Christian-Albrechts University Kiel, Kiel, Germany. FAU - Kulle, A E AU - Kulle AE AD - Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University Hospital Schleswig-Holstein, Christian-Albrechts University Kiel, Kiel, Germany. FAU - Laban, N AU - Laban N AD - Medical Faculty Skopje, Skopje, Republic of Macedonia. FAU - Polenakovic, M AU - Polenakovic M AD - Research Centre for Genetic Engineering and Biotechnology "Georgi D. Efremov," Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia. FAU - Plaseska-Karanfilska, D AU - Plaseska-Karanfilska D AD - Research Centre for Genetic Engineering and Biotechnology "Georgi D. Efremov," Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia. FAU - Sanna-Cherchi, S AU - Sanna-Cherchi S AD - Division of Nephrology, Columbia University, New York, NY, USA. FAU - Kostovski, M AU - Kostovski M AD - Medical Faculty Skopje, Skopje, Republic of Macedonia.