ESHG 2024 Poster: Nuclear Mitochondrial DNA disruption in KLHL10 gene causes Spermatogenic Failure – a Case Study


Mitochondrial DNA (mtDNA) translocation into the nuclear genome, also known as Nuclear Mitochondrial DNA insertions (NUMT), is an extremely rare genetic event that may disrupt a protein-coding gene and cause disease. How exactly NUMTs occur is poorly understood. It is suggested that key mechanisms involve a combination of abnormal mitochondria degradation and non-homologous end-joining DNA repair at nuclear double-strand breaks.

NUMTs have been implicated in human biology and pathology, including aging, cancer, and Mendelian disease. Up to date, only a handful of disease-causing NUMTs have been described. However, recent studies show that NUMTs variation is continuously misreported as mitochondrial mutations in patients.

Here we present a rare case of spermatogenic failure in which a NUMT disrupts KLHL10 through insertion into exon 3 of the gene. Autosomal dominant pathogenic variants in the gene have been reported to cause oligozoospermia.

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