Founder effect of the TTTCA repeat insertions in SAMD12 causing BAFME1

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Benign adult familial myoclonic epilepsy type 1 (BAFME1) is a rare genetic epilepsy.
• Previous studies linked BAFME1 in Japanese and Chinese families to pentanucleotide repeat expansions in the SAMD12 gene.

Purpose of the Study:

• To investigate the genetic cause of BAFME1 in a Thai family.
• To determine if SAMD12 repeat expansions are associated with BAFME1 in this new population.

Main Methods:

• Microsatellite analysis to suggest linkage to the BAFME1 chromosomal region (8q24).
• Long-read whole-genome sequencing to identify the specific repeat expansion in SAMD12.
• Repeat-primed PCR and long-range PCR to confirm segregation of the expansion with the disease.

Main Results:

• A Thai family with six affected members diagnosed with BAFME1 was identified.
• Pentanucleotide repeat expansions, specifically (TTTTA)446(TTTCA)149 in SAMD12 intron 4, were found in affected individuals.
• The identified repeat expansion segregated with the disease phenotype within the family.

Conclusions:

• This study reports the first non-Japanese and non-Chinese family with BAFME1.
• The findings confirm that SAMD12 pentanucleotide repeat expansions are a cause of BAFME1 in diverse ethnic groups.
• SNP array analysis suggests a common ancestral origin for the BAFME1-associated repeat expansion, estimated to have arisen approximately 12,000 years ago.