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  • Brief Communication
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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.

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We thank N. Watanabe, T. Miyama, M. Sato, S. Sugimoto, and K. Takabe for technical assistance. We also thank Edanz ( for editing a draft of this manuscript. This work was supported by the Japan Agency for Medical Research and Development (AMED) under grant numbers JP23ek0109674, JP23ek0109549, JP23ek0109617, JP23ek0109648 (NM); JSPS KAKENHI under grant numbers 21K15704 (TT), JP22K15646 (KH), JP23K07229 (YU), JP21K07869 (EK), JP23K15353 (NT), JP22K15901 (AF), JP20K07316 (KM), JP23H02829 (SM), and JP23H02877, JP23K18278 (TM); and the Takeda Science Foundation (TM and NM).

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Conceptualization: TM, HA, NM; investigation: TM, EK, SK, HF, NT, YU, KH, AF, KM, SM; resources: TT, HA; visualization: TM; writing—original draft: TM, NM; writing—review and editing: TM, NM; All authors read and approved the final manuscript before submission.

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Correspondence to Takeshi Mizuguchi or Naomichi Matsumoto.

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The authors declare no competing interests.

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This study was approved by the Institutional Review Boards of Yokohama City University School of Medicine. Written informed consent was obtained from all participants.

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Mizuguchi, T., Toyota, T., Koshimizu, E. et al. Complete SAMD12 repeat expansion sequencing in a four-generation BAFME1 family with anticipation. J Hum Genet 68, 875–878 (2023).

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