What question did this study set out to answer?

The aim is to discuss a novel NR0B1 variant linked to congenital adrenal hypoplasia and its clinical implications.

February 27, 2026Open Access

A novel NR0B1 pathogenic variant in congenital adrenal hypoplasia presenting with azoospermia and normal testosterone

Key Points

The aim is to discuss a novel NR0B1 variant linked to congenital adrenal hypoplasia and its clinical implications.
Case report of a 23-year-old male with X-linked congenital adrenal hypoplasia.
Conducted whole-exome sequencing to identify genetic variants.
Clinical assessment included testosterone levels and fertility evaluation.
Identified a novel pathogenic NR0B1 variant (c.625C>T; p.Gln209).
Patient presented with azoospermia but normal testosterone levels.
Findings suggest Sertoli cell dysfunction as a mechanism of infertility.

Abstract

Abstract X-linked congenital adrenal hypoplasia (X-linked AHC) is a rare endocrine disorder causing primary adrenal insufficiency (PAI) and often associated with hypogonadotropic hypogonadism (HH). We report a 23-year-old male with early-onset PAI, normal puberty, and azoospermia despite normal testosterone levels. Whole-exome sequencing revealed a novel NR0B1 pathogenic variant (c.625CT; p.Gln209). NR0B1, also known as DAX1, is critical for adrenal and gonadal development, and animal models suggest that Sertoli cell dysfunction is a key mechanism of infertility, occurring independently of gonadotropin or androgen deficiencies. Taken together, this case expands the clinical spectrum of NR0B1-related disease and underscores the importance of early genetic testing and consideration of this diagnosis even in patients with X-linked AHC and atypical presentations.

A novel NR0B1 pathogenic variant in congenital adrenal hypoplasia presenting with azoospermia and normal testosterone

Key Points

Abstract

Cite This Study