<abstract xmlns="http://www.w3.org/1999/xhtml"><p>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, <italic>SOX3</italic> emerged as the main phenotypic driver. This is the fifth case reporting a genomic imbalance involving the <italic>SOX3</italic> gene in a 46,XX SRY-negative male, and the first with associated renal malformations. Our data provide plausible links between <italic>SOX3</italic> gene dosage and kidney malformations. It is noteworthy that the current and reported <italic>SOX3</italic> 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 <italic>SOX3</italic> gene duplications with DNA microarrays.</p></abstract>

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.

Duplication of the <italic>SOX3</italic> 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

Balkan Journal of Medical Genetics

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Duplication of the  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

Disorders of sex development (DSD) are a group of rare conditions characterized by discrepancy between chromosomal sex, gonads and external genitalia....

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

Article Category: Case Report

Published Online: Aug 28, 2019

Page range: 81 - 88

DOI: https://doi.org/10.2478/bjmg-2019-0006

Keywords
Congenital anomalies of kidneys and the urinary tract (CAKUT), Copy number variations (CNVs), Disorders of sex development (DSD)

© 2019 Tasic V, Mitrotti A, Riepe FG, Kulle AE, Laban N, Polenakovic M, Plaseska-Karanfilska D, Sanna-Cherchi S, Kostovski M, Gucev Z, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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

Article Category: Case Report

Published Online: Aug 28, 2019

Page range: 81 - 88

DOI: https://doi.org/10.2478/bjmg-2019-0006

KeywordsCongenital anomalies of kidneys and the urinary tract (CAKUT), Copy number variations (CNVs), Disorders of sex development (DSD)

© 2019 Tasic V, Mitrotti A, Riepe FG, Kulle AE, Laban N, Polenakovic M, Plaseska-Karanfilska D, Sanna-Cherchi S, Kostovski M, Gucev Z, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
Congenital anomalies of kidneys and the urinary tract (CAKUT), Copy number variations (CNVs), Disorders of sex development (DSD)