Identification of New Repeat Expansion Diseases

ABSTRACT Through a genetic study of benign adult familial myoclonus epilepsy (BAFME) type 1, TTTCA and TTTTA repeat expansions have been identified in intron 4 of SAMD12 . Lengths of expanded repeats inversely correlated with age at onset of epilepsy. Gain‐of‐toxic function mechanisms are suggested by the presence of UUUCA‐repeat‐containing RNA foci. From families with BAFME who did not have repeat expansions in SAMD12 , we identified expanded TTTCA and TTTTA repeats in TNRC6A and RAPGEF2 . These findings indicated a strong correlation between the repeat motif and the phenotype, leading to the identification of other types of BAFME. We then conducted genetic analysis of neuronal intranuclear inclusion disease (NIID), oculopharyngeal myopathy with leukoencephalopathy (OPML), and oculopharyngodistal myopathy (OPDM). From the observation that NIID, OPML, and OPDM, in addition to fragile X‐associated tremor/ataxia syndrome, have shared clinical features, a direct search for CGG repeat expansions successfully led to the identification of the causative genes. Here, I review recent studies on repeat expansions.