• PMID: 21227944
• Gene Name: DAX1
• Condition: X-linked congenital adrenal hypoplasia (AHC)
• Association: Birth after TESE-ICSI in a man with hypogonadotropic hypogonadism and congenital adrenal hypoplasia linked to a DAX-1 (NR0B1) mutation.
• Mutation: DAX1 mutation (c.1210C>T)
• Population size: 1
• Population details: 1 X-linked congenital adrenal hypoplasia (AHC)
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: X-linked congenital adrenal hypoplasia (AHC)

Birth after TESE-ICSI in a man with hypogonadotropic hypogonadism and congenital adrenal hypoplasia linked to a DAX-1 (NR0B1) mutation

Frapsauce C, Ravel C, Legendre M, Sibony M, Mandelbaum J, Donadille B, Achermann JC, Siffroi JP, Christin-Maitre S.

DAX1/NR0B1 mutations are responsible for X-linked congenital adrenal hypoplasia (AHC) associated with hypogonadotropic hypogonadism (HH). Few data are available concerning testicular function and fertility in men with DAX1 mutations. Azoospermia as well as failure of gonadotrophin treatment have been reported. We induced spermatogenesis in a patient who has a DAX1 mutation (c.1210C>T), leading to a stop codon in position 404 (p.Gln404X). His endocrine testing revealed a low testosterone level at 1.2 nmol/l (N: 12-40) with low FSH and LH levels at 2.1 IU/l (N: 1-5 IU/l) and 0.1 IU/l (N: 1-4 IU/l), respectively. Baseline semen analysis revealed azoospermia. Menotropin (Menopur(®):150 IU, three times weekly) and human chorionic gonadotrophin (1500 IU, twice weekly) were used. After 20 months of treatment, as azoospermia persisted, bilateral multiple site testicular biopsies were performed. Histology revealed severe hypospermatogenesis. Rare spermatozoa were extracted from the right posterior fragment and ICSI was performed. Four embryos were obtained and, after a frozen-thawed single-embryo transfer, the patient's wife became pregnant and gave birth to a healthy boy. We report the first case of paternity after TESE-ICSI in a patient with DAX1 mutation, giving potential hope to these patients to father non-affected children. Furthermore, this case illustrates the fact that patients with X-linked AHC have a primary testicular defect in addition to HH. FAU - Frapsauce, C AU - Frapsauce C AD - UPMC, AP-HP, Hôpital Tenon, Service de Biologie de la Reproduction, 75020 Paris, France. FAU - Ravel, C AU - Ravel C FAU - Legendre, M AU - Legendre M FAU - Sibony, M AU - Sibony M FAU - Mandelbaum, J AU - Mandelbaum J FAU - Donadille, B AU - Donadille B FAU - Achermann, J C AU - Achermann JC FAU - Siffroi, J-P AU - Siffroi JP