SOX3 is located on the X-chromosome (Xq27.1) and encodes a SRY-related protein that acts as a developmental transcription factor. Copy Number Variations (losses and gains), mutations of polyalanine stretches (deletions or expansions) and missense mutations of SOX3 have been associated with growth hormone deficiency with incomplete penetrance, hypogonadism, differences of sexual development and variable additional endocrine disorders (MIM #312000 and #300123). We report on a family in which three male members (aged 40 years; 4.3 years and 6.3 years at presentation) with growth hormone deficiency and cryptorchidism/hypogonadism. Array CGH analyses revealed a novel 3.3 Mb duplication in Xq26.3-q27.1 that was located 86 kb downstream of SOX3 on the X-chromosome in all three patients. Female carriers of the duplication were detected, but are clinically healthy. We hypothesize that this duplication exerts a position effect on SOX3 transcription. Further investigations in familiar growth hormone deficiency, cryptorchidism, and ectopic pituitary gland must be performed to learn more about the role of the copy number variations in the vicinity of SOX3.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology