CIC de novo loss of function variants contribute to cerebral folate deficiency by downregulating FOLR1 expression.

ABSTRACT: Background Cerebral folate deficiency (CFD) syndrome is characterised by a low concentration of 5-methyltetrahydrofolate in cerebrospinal fluid, while folate levels in plasma and red blood cells are in the low normal range. Mutations in several folate pathway genes, including FOLR1 (folate receptor alpha, FRα), DHFR (dihydrofolate reductase) and PCFT (proton coupled folate transporter) have been previously identified in patients with CFD. Methods In an effort to identify causal mutations for CFD, we performed whole exome sequencing analysis on eight CFD trios and identified eight de novo mutations in seven trios. Results Notably, we found a de novo stop gain mutation in the capicua (CIC) gene. Using 48 sporadic CFD samples as a valida

SUBMITTER: Cao X 

PROVIDER: S-EPMC7895856 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature