Anvar Zahra, Jafarpour Farnoosh, Jahromi Bahia Namavar, Riccio Andrea, Nasr-Esfahani Mohammad Hossein, Cubellis Maria Vittoria
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, USA.
Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas, USA.
Mol Genet Genomic Med. 2025 Jan;13(1):e70051. doi: 10.1002/mgg3.70051.
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.
KHDC3L基因编码皮层下母体复合体（SCMC）的一个组成部分。该基因的双等位基因突变导致5%-10%的双亲性葡萄胎（BiHM），并且在复发性流产（RPL）女性中已鉴定出少数KHDC3L的母源缺失。
在本研究中，我们有一名有10次妊娠或新生儿丢失病史的患者，包括自然流产、新生儿死亡和葡萄胎妊娠。进行全外显子组测序（WES）用于基因诊断检测。
我们在KHDC3L的起始密码子中发现了一个纯合有害变异（c.1A>G，p.M1V），这可能导致不翻译或产生截短蛋白。
这是KHDC3L基因母源功能丧失变异在经历各种类型妊娠丢失患者中的首次报道。本病例报告拓宽了对KHDC3L致病变异和表型谱的理解，与其在人类植入前和植入后发育中的关键作用一致。
