A Homozygous Variant in DMRTB1 Is Associated With Non‐Obstructive Azoospermia in Humans

Non-obstructive azoospermia (NOA) represents the most severe form of male infertility, and the pathogenesis in partial patients can be attributed to endocrine dysfunction or heritable genetic variants. Although the application of whole-exome sequencing (WES) has facilitated the identification of numerous pathogenic genes associated with NOA, the genetic etiology of a significant proportion of cases remains elusive. In this study, we identified an NOA patient carrying a novel variant in DMRTB1 (c.792-797del, p.265-266del). The variant was rare in public databases and predicted to be likely pathogenic according to the American College of Medical Genetics (ACMG) guidelines. Structural modeling performed by SWISS-MODEL revealed the localized structural perturbations within residues 254-266, which may induce functional alterations. Histological analysis (H&E staining) of the testicular tissue revealed a complete absence of mature sperm within the seminiferous tubules, which is consistent with the essential role of this gene demonstrated in Dmrt6 knockout mice. Our findings demonstrate that the identified DMRTB1 variant is closely associated with the pathogenesis of NOA, thereby providing valuable genetic evidence for the diagnosis of NOA.