[Molecular genetics of benign adult familial myoclonus epilepsy]

Abstract

Benign adult familial myoclonus epilepsy (BAFME) is an autosomal dominantly inherited disease characterized by infrequent seizures and tremorous myoclonus. The disease is also called familial adult myoclonic epilepsy (FAME) or familial cortical myoclonic tremor with epilepsy (FCMTE). Although the causes of BAFME had been unknown for a long, we identified TTTCA and TTTTA repeat expansions in intron 4 of SAMD12 as a cause of BAFME type 1. We also found TTTCA and TTTTA repeat expansions in TNRC6A and RAPGEF2 also cause the disease (BAFME types 6 and 7, respectively), thus proposing a concept of repeat motif-phenotype correlation. After that, TTTCA and TTTTA repeat expansions in STARD7, MARCHF6, YEATS2, and RAI1 have been identified as causes of BAFME types 2, 3, 4, and 8. The findings further supported the concept. The involvement of RNA-mediated toxicity, particularly of UUUCA repeats, is assumed to be the pathomechanism of this disease. The next step will be understanding the molecular pathomechanism of BAFME and identifying molecular targets of more efficient therapeutic approaches.

Keywords: RNA toxicity; benign adult familial myoclonus epilepsy; intron; repeat expansions; repeat motif–phenotype correlation.