Abstracts

Rationale:
Familial adult myoclonic epilepsy type 1 (FAME1) is an autosomal dominant disorder characterized by adult onset cortical tremor, myoclonus and infrequent epilepsy with a slowly progressive course. The genetic cause of FAME1 was discovered in 2018 by Ishiura et al. due to a complex pentanucleotide repeats TTTTA expansion and TTTCA insertion in the intron of SAMD12 gene. Since then, FAME1 has been found in families in Japan, China, Thailand, Sri Lanka, Indian and even in Canada with European descent. Here, we report the first two Taiwanese FAME1 families.









Methods: All participants were recruited at the Chang Gung Memorial Hospitals and evaluated by an experienced neurologist. Medical records and clinical investigations were also reviewed. After informed consent, DNA was extracted and repeat-prime polymerase chain reaction (RP-PCR) was performed on all participants at Kaohsiung Chang Gung Memorial Hospital. Haplotype analysis was performed using Sanger sequencing to genotype relevant single nucleotide polymorphisms (SNPs). A cohort of healthy controls (n=311) was also used to evaluate the allele frequency of (TTTTA)exp and (TTTCA)ins in the Taiwanese population.

Results: Two autosomal dominant FAME1 families were identified, both have the characteristic (TTTTA)exp(TTTCA)ins configuration in the intron 4 of SAMD12 gene on RP-PCR. Tremor onset ranged from 15-44 years old, mostly affecting the upper limbs during action and resting. Seizure onset ranged from 19-42 years old, usually onset later than tremor. There were a few affected individuals only presented with tremor/myoclonus. Neuroimaging study were normal or showed unspecific findings. Most patients had a stationary or slowly progressive course and were pharmacoresponsive to antiseizure medications. Haplotype analysis revealed that both families have the previously reported common founder haplotype. We also found (~4%) 12/311 of normal healthy controls also have (TTTTA)exp > 40 repeats, but none have (TTTCA)ins.

Conclusions:
FAME1 can also be found in Taiwanese population, which shares the same common haplotype, probably coming from the same founder. TTTTA motif expansion can be seen in normal population, which suggests that the presence of TTTCA motif insertion is more pathognomonic to FAME.









Funding: Chang Gung Medical Foundation, National Science and Technology Council, National Health and Research Institute, Taiwan