# Phenotypic and genotypic characterization of familial adult myoclonus epilepsy in a Chinese case series

## TL;DR

This study characterizes a genetic disorder in Chinese patients, finding unstable DNA repeats linked to symptoms and age of onset.

## Contribution

The study provides a detailed genetic and clinical analysis of familial adult myoclonus epilepsy in a Chinese population using HiFi long-read sequencing.

## Key findings

- All patients were diagnosed with familial adult myoclonus epilepsy type 1, with highly unstable TTTCA repeat sizes.
- An inverse correlation was found between the number of TTTCA repeats and age of onset.
- Clinical anticipation was observed for tremor and seizure symptoms.

## Abstract

Familial adult myoclonus epilepsy is a type of repeat expansion disorders caused by insertion of the causative pentanucleotide TTTCA repeat into an intronic polymorphic TTTTA repeat in different genes. We aimed to characterize the clinical features and elucidate the exact genetic basis of TTTTA/TTTCA repeat expansion in familial adult myoclonus epilepsy from mainland China. Eighty-five individuals including 36 patients and 49 normal phenotype relatives from seven pedigrees with familial adult myoclonus epilepsy, were recruited in a case series from mainland China. Repeat-primed PCR was used for initial screening. Long-range PCR-based enrichment, followed by targeted deep HiFi long-read sequencing, was performed to precisely clarify the detailed information of causative pentanucleotide TTTTA/TTTCA repeat expansion. The results indicated there exists obvious clinical heterogeneity both within and between families in our patient group. All patients were genetically diagnosed with familial adult myoclonus epilepsy type 1. The number of pentanucleotide repeats was extremely unstable, with median TTTCA repeat sizes ranging from 10 to 647 in the affected members of our case series under a mean sequence depth of coverage above 50 000. The [(TTTTA)exp (TTTCA)exp] motif was the only configuration of expanded SAMD12 repeats in our case series. An inverse correlation was found between the age of onset and the number of TTTCA repeats and the total number of TTTTA/TTTCA repeats. Clinical anticipation was observed for tremor and seizure symptoms. However, we did not demonstrate a link between parent-offspring differences in repeat sizes and their changes in age of onset. In summary, we determined the nature of the expanded repeats and a reliable phenotype-genotypic correlation in our case series of familial adult myoclonus epilepsy through targeted deep HiFi long-read sequencing technologies.

Zeng et al. characterize 36 patients with familial adult myoclonus epilepsy type 1 using HiFi long-read sequencing. They delineated clinical features, identified highly unstable expanded SAMD12 TTTTA/TTTCA repeats, and demonstrated an inverse correlation between repeat size and age of onset. The study advances the understanding of this disorder.

Graphical Abstract