Impaired DNA methylation in oocytes with a mutation in KHDC3L causing recurrent hydatidiform mole

Mutations in components of the subcortical maternal complex (SMC) of the human oocyte are enigmatically associated with DNA methylation abnormalities specifically at imprinted genes in conceptuses, but the developmental timing, genomic extent and mechanistic details of these defects are unknown. Here, we show, by single-cell bisulphite sequencing, that mutation in human KHDC3L that causes recurrent hydatidiform mole results in a genome-wide deficit of de novo methylation in oocytes. BS-seq of 5 oocytes and 1 preimplantation embryo of patient D with a KHDC3L mutation and a history of 2 biparental molar pregnancies