Complete SAMD12 repeat expansion sequencing in a four-generation BAFME1 family with anticipation

Benign adult familial myoclonic epilepsy type 1 (BAFME1) is an autosomal dominant, adult-onset neurological disease caused by SAMD12 repeat expansion. In BAFME1, anticipation, such as the earlier onset of tremor and/or seizures in the next generation, was reported. This could be explained by intergenerational repeat instability, leading to larger expansions in successive generations. We report a four-generation BAFME1-affected family with anticipation. Using Nanopore long-read sequencing, detailed information regarding the sizes, configurations, and compositions of the expanded SAMD12 repeats across generations was obtained. Unexpectedly, a grandmother-mother-daughter triad showed similar repeat structures but with slight repeat expansions, despite quite variable age of onset of seizures (range: 52-14 years old), implying a complex relationship between the SAMD12 repeat expansion sequence and anticipation. This study suggests that different factor(s) from repeat expansion could modify the anticipation in BAFME1.

Automated summary

Benign adult familial myoclonic epilepsy type 1 (BAFME1) is an adult-onset neurological disease caused by SAMD12 repeat expansion. Anticipation, characterized by earlier onset of tremor and/or seizures in the next generation, was observed in BAFME1. Through Nanopore long-read sequencing, detailed information about the expanded SAMD12 repeats across generations was obtained. Surprisingly, a grandmother-mother-daughter trio showed similar repeat structures with slight expansions, despite a wide range of onset ages, indicating a complex relationship between SAMD12 repeat expansion sequence and anticipation. This study suggests that factors other than repeat expansion may modify anticipation in BAFME1.