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, 19 (2), 108-12

A Korean Boy With 46,XX Testicular Disorder of Sex Development Caused by SOX9 Duplication


A Korean Boy With 46,XX Testicular Disorder of Sex Development Caused by SOX9 Duplication

Gyung Min Lee et al. Ann Pediatr Endocrinol Metab.


The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare form of DSD and clinical phenotype shows complete sex reversal from female to male. The sex-determining region Y (SRY) gene can be identified in most 46,XX testicular DSD patients; however, approximately 20% of patients with 46,XX testicular DSD are SRY-negative. The SRY-box 9 (SOX9) gene has several important functions during testis development and differentiation in males, and overexpression of SOX9 leads to the male development of 46,XX gonads in the absence of SRY. In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans. Here, we report a 4.2-year-old SRY-negative 46,XX boy with complete sex reversal caused by SOX9 duplication for the first time in Korea. He showed normal external and internal male genitalia except for small testes. Fluorescence in situ hybridization and polymerase chain reaction (PCR) analyses failed to detect the presence of SRY, and SOX9 intragenic mutation was not identified by direct sequencing analysis. Therefore, we performed real-time PCR analyses with specific primer pairs, and duplication of the SOX9 gene was revealed. Although SRY-negative 46,XX testicular DSD is a rare condition, an effort to make an accurate diagnosis is important for the provision of proper genetic counseling and for guiding patients in their long-term management.

Keywords: Disorders of sex development; Sex determining region Y-box 9; Sex-determining region gene on Y; XX male syndrome.

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.


Fig. 1
Fig. 1
(A) The genitalia photograph of the patient was taken at 4.2 years of age. His external genitalia show complete male phenotypes without ambiguity. (B) Normal internal genital organs are visible, and there is no evidence of female genital organs on the T2-weighted magnetic resonance image.
Fig. 2
Fig. 2
Results of real-time polymerase chain reaction analysis using two sets of specific primer pairs (A, proximal primer pair; B, distal primer pair) show the increased copy number of SOX9 in the patient (approximately 1.5 times) compared with a control male. RQ, relative quantification.

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