Y-chromosomal gains in MOGHE

Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is an underrecognized pediatric cortical lesion associated with somatic X-linked SLC35A2 variants in approximately 50% of individuals. Erica's new studies identified Y-chromosomal material in the other 50% of patients with MOGHE, confirmed by CNV plotting, PCR and FISH, and associated with lesional tissue. Exploratory stratification of the cohort by SLC35A2 status and Y-chromosome gain revealed a tendency toward earlier seizure onset, multilobar involvement, and cognitive impairment in patients carrying even both SLC35A2 mutations and Y-chromosome gain. Although the root cause, biological consequence, and clinical significance of brain somatic Y-chromosomal gain remain to be further clarified, our findings identify a previously unrecognized genomic feature of MOGHE and provide a rationale for future research in MOGHE cohorts. We congratulate Erica for this excellent achievement.