Maria Vittoria Cubellis

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

ABSTRACTBackgroundThe 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).MethodIn 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.ResultsWe 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.ConclusionThis 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.