A homozygous KASH5 frameshift mutation causes diminished ovarian reserve, recurrent miscarriage, and non-obstructive azoospermia in humans.

ABSTRACT: The meiosis-specific LINC complex, composed of the KASH5 and SUN1 proteins, tethers the moving chromosomes to the nuclear envelope to facilitate homolog pairing and is essential for gametogenesis. Here, we applied whole-exome sequencing for a consanguineous family with five siblings suffering from reproductive failure, and identified a homozygous frameshift mutation in KASH5 (c.1270_1273del, p.Arg424Thrfs*20). This mutation leads to the absence of KASH5 protein expression in testes and non-obstructive azoospermia (NOA) due to meiotic arrest before the pachytene stage in the affected brother. The four sisters displayed diminished ovarian reserve (DOR), with one sister never being pregnant but still having dominant follicle at 35 years old and three sisters suffering from at least 3 m

SUBMITTER: Hou X 

PROVIDER: S-EPMC9971600 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature