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.