A Maternal Loss-of-Function Variant in KHDC3L Gene Causes a Range of Adverse Pregnancy Outcomes: A Case Report

The KHDC3L gene encodes a component of the subcortical maternal complex (SCMC). Biallelic mutations in this gene cause 5%-10% of biparental hydatidiform moles (BiHM), and a few maternal deletions in KHDC3L have been identified in women with recurrent pregnancy loss (RPL).

In this study, we had a patient with a history of 10 pregnancy or neonatal losses, including spontaneous abortions, neonatal deaths, and molar pregnancy. Whole-exome sequencing (WES) was performed for genetic diagnostic testing.

We found a homozygous deleterious variant in the start codon of KHDC3L (c. 1A>G, p.M1V), which probably results in non-translation or the production of a truncated protein.

This is the first report of a maternal loss-of-function variant in KHDC3L gene in a patient experiencing various types of pregnancy loss. This case report broadens the understanding of KHDC3L's pathogenic variants and phenotypic spectrum, consistent with its crucial role during human pre- and post-implantation development.