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TTTCA repeat expansion causes familial cortical myoclonic tremor with epilepsy
Author(s) -
Lei X. X.,
Liu Q.,
Lu Q.,
Huang Y.,
Zhou X. Q.,
Sun H. Y.,
Wu L. W.,
Cui L. Y.,
Zhang X.
Publication year - 2019
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.13848
Subject(s) - generalized epilepsy , epilepsy , medicine , clonazepam , myoclonic epilepsy , pediatrics , family history , myoclonic jerk , epilepsy syndromes , electroencephalography , anesthesia , psychiatry
Background and purpose The aim was to investigate whether abnormal TTTTA and TTTCA repeat expansions in introns of SAMD12 , TNRC 6A and RAPGEF 2 are involved in the pathogenesis of familial cortical myoclonic tremor with epilepsy ( FCMTE ). Methods Five families diagnosed with FCMTE were included in the current genetic analysis. Whole‐exome sequencing was performed in selected patients of each family. TTTTA and TTTCA expansions were examined by repeat‐primed polymerase chain reaction. The clinical features of FCMTE were elicited as defined by the common genetic mechanism of 14 patients. Results Abnormal TTTCA expansion was identified and co‐segregated in all five FCMTE families, four inserted in SAMD 12 and one in RAPGEF 2 . The insertion of expanded TTTCA was not found in 116 control alleles. TTTTA expansion in SAMD 12 was detected in 90.9% (10/11) of patients or mutation carriers; TTTTA expansion in RAPGEF 2 was not found. The onset age of myoclonic tremor was 27.4 ± 5.9 (19–37) and epilepsy usually presented around age 34. Focal and generalized seizures were witnessed with various origins recorded by electroencephalogram. Cognitive deficits were not common within the first 3 years after epilepsy onset. Emotional instability was reported by most patients. No patients showed any cerebellar deficits. Valproate added with clonazepam is effective in controlling seizures but cannot guarantee a complete remission of tremor. Repeat length showed intergenerational instability and was inversely correlated with age at onset of myoclonic tremor and epilepsy. Conclusions TTTCA expansion insertion is associated with FCMTE in Chinese families. The homogenous genetic mechanism allowed for a higher precision of FCMTE description.