Case presentation An 11 old patient with hypoplasia of the right kidney and hypospadias was found to be SRY negative, 46, XX. His parents and younger sister were healthy. His intelligence was normal (IQ 92) and he had no other anomalies. The behavior, growth and development were all normal. His testes were >4ml and the penis was 5 cm. Ultrasound and MRI did not show internal female genitals, while confirming right kidney hypoplasia (as did the DMSA scan).
ACTH test showed normal basal and stimulated 17OH-progesterone excluding a form of 46XX DSD due to 21-hydroxylase deficiency. 11-DOC and 11S were normal at both baseline and after ACTH stimulation, excluding 11-hydroxylase deficiency. Cortisol levels were in the mid normal range at baseline and responded to stimulation, excluding primary adrenal insufficiency. Androstenedione,
The hCG test found testosterone in the low normal range for male sex and age at baseline. It rised up to 146 ng/mL indicating the presence of functional Leydig cells targeted by hCG. The stimulated ratio T:DHT was 5.6, not supporting 5 alpha-reductase deficiency.
SNP array for copy number variations (CNV’s) showed a unique 550 kb duplication involving SOX3, RP1–177G6, and CDR1 genes, and the microRNA MIR320D2. This CNV was absent in 13,839 controls.
Conclusions A SRY negative 46, XX male with renal hypodysplasia was found to have an exceedingly rare duplication involving the SOX-3 gene, proving its role in sex determination and suggesting its evolvement in kidney development.