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

Journal of Human Genetics volume 68, pages 875–878 (2023)Cite this article

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Abstract

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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Acknowledgements

We thank N. Watanabe, T. Miyama, M. Sato, S. Sugimoto, and K. Takabe for technical assistance. We also thank Edanz (https://jp.edanz.com/ac) 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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Authors and Affiliations

  1. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan

    Takeshi Mizuguchi, Eriko Koshimizu, Shinichi Kameyama, Hiromi Fukuda, Naomi Tsuchida, Yuri Uchiyama, Kohei Hamanaka, Atsushi Fujita, Kazuharu Misawa, Satoko Miyatake & Naomichi Matsumoto

  2. Department of Neurology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, 807-8555, Japan

    Tomoko Toyota & Hiroaki Adachi

  3. Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan

    Hiromi Fukuda

  4. Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, 236-0004, Japan

    Naomi Tsuchida & Yuri Uchiyama

  5. Department of Clinical Genetics, Yokohama City University Hospital, Yokohama, 236-0004, Japan

    Satoko Miyatake

Authors
  1. Takeshi Mizuguchi
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  2. Tomoko Toyota
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  3. Eriko Koshimizu
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  9. Atsushi Fujita
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  10. Kazuharu Misawa
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  11. Satoko Miyatake
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  12. Hiroaki Adachi
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  13. Naomichi Matsumoto
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Contributions

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.

Corresponding authors

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). https://doi.org/10.1038/s10038-023-01187-5

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  • DOI: https://doi.org/10.1038/s10038-023-01187-5

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