Ann Pediatr Endocrinol Metab.  2014 Jun;19(2):108-112. 10.6065/apem.2014.19.2.108.

A Korean boy with 46,XX testicular disorder of sex development caused by SOX9 duplication

Affiliations
  • 1Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea. jmko@snu.ac.kr
  • 2Research Coordination Center for Rare Diseases, Seoul National University Children's Hospital, Seoul, Korea.

Abstract

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.

Keyword

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

MeSH Terms

46, XX Testicular Disorders of Sex Development
Diagnosis
Disorders of Sex Development
Female
Fluorescence
Genes, sry
Genetic Counseling
Genitalia, Male
Gonads
Humans
In Situ Hybridization
Korea
Male
Phenotype
Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Sexual Development*
Testis

Figure

  • 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 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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