ClinVar

In affected members of a family with autosomal dominant rolandic epilepsy, mental retardation, and speech dyspraxia (FESD; 245570), originally reported by Scheffer et al. (1995), Carvill et al. (2013) identified a heterozygous G-to-A transition in intron 4 of the GRIN2A gene (c.1007+1G-A), predicted to result in the skipping of exon 4 and premature termination (Phe139IlefsTer15). The mutation was not found in 6,500 control exomes. The same heterozygous mutation was also found in a father and son with epileptic encephalopathy with continuous spike and wave in slow-wave sleep. Analysis of patient cells showed that the mutant transcript underwent nonsense-mediate mRNA decay. Both of the families were of European descent, and haplotype analysis indicated a founder effect. The findings suggested that GRIN2A mutations can cause a spectrum of epilepsy-aphasia phenotypes.

Lemke et al. (2013) identified a heterozygous c.1007+1G-A in 7 affected individuals from 3 unrelated families and in a singleton individual, all with variable manifestations of epilepsy, including Landau-Kleffner syndrome, continuous spike and waves during slow-wave sleep, atypical benign partial epilepsy, and benign epilepsy with centrotemporal spikes. Lemke et al. (2013) suggested that additional modifying factors might explain the phenotypic variability.