The DAX1 mutation in a patient with hypogonadotropic hypogonadism and adrenal hypoplasia congenita causes functional disruption of induction of spermatogenesis

Abstract

Hypogonadotropic hypogonadism (HH) associated with adrenal hypoplasia congenita (AHC) is a very rare syndrome caused by mutation of DAX1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome) [19]. The DAX1 is located on the chromosome X (Xp21.3–21.2) and contains two exons. It encodes a 470-amino acid protein which belongs to the nuclear hormone receptor superfamily (called DAX1). DAX1 is expressed in the adrenal cortex, pituitary and hypothalamus, gonadal cells such as Leydig and Sertoli cells, theca and granulosa cells and in germ cells [15, 26]. Patients with HH due to DAX1 mutation exhibited azoospermia [4, 5, 17, 24]. Results of spermatogenesis induction using exogenous gonadotropin are unsatisfactory [4, 17, 24]. However, Frapsauce et al. [5] has recently presented the first birth after successful assisted reproductive technique (ART) using TESE-ICSI in a man with HH and AHC linked to a DAX1 mutation. In this case, long period of gonadotropin treatment allowed for development of few mature spermatozoa obtained from testicular biopsy and used for ICSI [5]. Here, we report clinical and immunohistochemical studies of patient with HH and AHC due to deletion of the second exon of the DAX1 in order to induce spermatogenesis by gonadotropins treatment.