Study of GRIN2A mutation in epilepsy-aphasia spectrum disorders / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To detect potential mutations of the glutamate receptor subunit (GRIN2A) gene and delineate the clinical-genetic characteristics of patients with epilepsy-aphasia spectrum (EAS) disorders.</p><p><b>METHODS</b>One hundred twenty two patients with Landau-Kleffner syndrome (LKS), epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS), benign childhood epilepsy with centrotemporal spikes (BECT) and BECT variants were recruited. Potential mutations of the GRIN2A gene were screened with Sanger sequencing. And clinical-genetic characteristics for all patients were analyzed.</p><p><b>RESULTS</b>The patients have included 9 LKS, 26 CSWS, 42 BECT variants and 45 BECT. The mean age of onset of seizure or aphasia was 5 years old (10 months to 11 years). Mutation screening has detected 4 possible pathogenic missense mutations including c.2278G>A (p.G760S), c.4153G>T (p.D1385Y), c.1364G>A (p.C455Y) and c.691T>C (p.C231R) in four unrelated probands, which comprised one case with LKS and three with BECT variants. The mutation rate was 11.1% (1/9) for LKS and 7.2% (3/42) for BECT variants. No GRIN2A mutation was found in the 26 patients with CSWS and 45 patients with BECT. Among the 122 probands, 25 (20.5%) patients without a GRIN2A mutation had a positive family history of febrile seizures or epilepsy.</p><p><b>CONCLUSION</b>GRIN2A mutation do exist in EAS patients, but with a relatively low rate. A proportion of EAS patients without a GRIN2A mutation have a positive family history, which suggested a complex mechanism for EAS.</p>