Identification of a Homozygous Nonsense Variant in KCTD19 Causing Meiotic Arrest and Non-obstructive Azoospermia in Humans

Abstract Background The genetic etiology of non-obstructive azoospermia (NOA) with maturation arrest (MA) remains incompletely characterized. Results Through whole-exome sequencing, a homozygous nonsense variant (c.119G > A, p.W40X) in KCTD19 was identified in two unrelated Chinese NOA patients. This variant disrupts the evolutionarily conserved BTB domain and leads to the absence of the KCTD19 protein. Histological analysis revealed complete absence of post-meiotic germ cells in probands’ testes, with spermatogenesis progressed to zygotene but failed to complete meiotic division. Conclusions Our findings demonstrate that bi-allelic loss-of-function variants in the meiotic gene KCTD19 cause complete MA. This study implicates an indispensable role of KCTD19 in meiotic prophase I, and expands the genetic spectrum underlying MA.