Identification of a Homozygous Nonsense Variant in KCTD19 Causing Meiotic Arrest and Non‐Obstructive Azoospermia in Humans

The genetic etiology of non‐obstructive azoospermia (NOA) characterized by maturation arrest (MA) remains incompletely understood. A homozygous nonsense variant (c.119G>A, p.W40X) in KCTD19 was identified in two unrelated probands with NOA. This variant disrupts the evolutionarily conserved BTB domain and leads to the absence of the KCTD19 protein. Histological analysis revealed a complete absence of post‐meiotic germ cells in the probands' testes, with spermatogenesis progressed into late prophase I (at least to the zygotene stage) but failed to complete meiotic division. Our findings demonstrate that bi‐allelic loss‐of‐function variants in the meiotic gene KCTD19 cause complete MA. This study highlights an indispensable role of KCTD19 in meiotic prophase I, and expands the genetic spectrum underlying male infertility.