Comprehensive genetic, clinical and electrophysiological studies of familial cortical myoclonic tremor with epilepsy 1 highlight the role of gene configurations

ObjectivesTwo configurations of TTTTA/TTTCA expansion in SAMD12 have been identified familial cortical myoclonic tremor with epilepsy type 1 (FCMTE1). This study investigated the clinical and neurophysiological features FCMTE1 their association patterns.MethodsIn total, 76 patients from 20 Chinese pedigrees were enrolled. Genetic (TTTTA/TTTCA configuration), (e.g., onset, medication, prognosis, anticipation) examination electroencephalogram magnetoencephalography) data evaluated, associations between these parameters analyzed.ResultsAll carried mutation, 19 displayed (TTTTA)exp(TTTCA)exp (type I) configuration (TTTTA)exp (TTTCA)exp(TTTTA)exp II) configuration. All manifested as progressive tremor, but symptoms carrying II more severe. The onset not generalized tonic clonic seizures anticipation generations 7 pedigrees, pedigree mutation did show anticipation. Nanopore sequencing showed that repeats expanded during maternal/offspring transmission (pedigree #7) shrank paternal/offspring #9). Magnetoencephalographic dipoles localized right frontal lobe near central sulcus 4 I on left side one patient mutation.SignificanceWe confirmed causative roles played by repeat gene FCTME1. Both length contribute to characteristics disease.