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Angelman syndrome with mosaic paternal uniparental disomy suggestive of mitotic nondisjunction

Journal of Human Genetics volume 68, pages 87–90 (2023)Cite this article

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A Correction to this article was published on 02 December 2022

This article has been updated

Abstract

Angelman syndrome (AS) is caused by the functional absence of the maternal ubiquitin-protein ligase E3A (UBE3A) gene. Approximately 5% of AS is caused by paternal uniparental disomy of chromosome 15 (UPD(15)pat), most of which is considered to result from monosomy rescue. However, little attention has focused on how UPD(15)pat occurs. We suggest the mitotic nondisjunction mechanism as a cause of UPD(15)pat in a six-year-old patient presenting with distinctive characteristics in line with AS. DNA methylation screening of 15q11-q13 showed a paternal band and a faint maternal band, suggestive of mosaic status. By trio-based microsatellite analysis, we confirmed a large proportion of UPD(15)pat cells and a small proportion of cells of biparental origin. Single nucleotide polymorphism (SNP) microarray revealed isodisomy of the entire chromosome 15. These results suggest that the UPD(15)pat of the patient resulted from mitotic nondisjunction, which may also be the cause of other cases of AS with UPD(15)pat.

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Change history

  • 30 November 2022

    The two terms, “methylation” and “unmethylation” were used wrongly with each other.

  • 02 December 2022

    A Correction to this paper has been published: https://doi.org/10.1038/s10038-022-01101-5

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Acknowledgements

We are grateful to the patients and their family for providing samples and clinical histories.

Funding

This research was supported by AMED under Grant Number JP21ek0109489 (S.S.).

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Authors and Affiliations

  1. Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Masanori Fujimoto, Yuji Nakamura, Toshihiko Iwaki, Emi Sato, Daisuke Ieda, Ayako Hattori & Shinji Saitoh

  2. Department of Child Neurology, Toyota Municipal Child Development Center Nozomi Clinic, Toyota, Japan

    Anna Shiraki

  3. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Anna Shiraki

  4. Department of Pediatrics, Central Hospital, Aichi Developmental Disability Center, Aichi, Japan

    Seiji Mizuno

Authors
  1. Masanori Fujimoto
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  2. Yuji Nakamura
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  3. Toshihiko Iwaki
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  4. Emi Sato
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  5. Daisuke Ieda
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  7. Anna Shiraki
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  8. Seiji Mizuno
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  9. Shinji Saitoh
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Contributions

All the authors contributed to the conception and design of the study. SS conceived and planned the experiments in consultation with YN and MF. YN and MF performed genetic analyses in collaboration with TI, ES, DI and AH. AS and SM performed clinical evaluation of the patient. MF wrote the manuscript with support from YN and SS. All authors critically reviewed and revised the manuscript draft and approved the final version for submission.

Corresponding author

Correspondence to Shinji Saitoh.

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Competing interests

The authors declare no competing interests.

Ethics approval

This study was approved by the institutional review board of Nagoya City University Graduate School of Medical Sciences, and written informed consent was obtained from the patient’s parents.

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The original online version of this article was revised: The two terms, “methylation” and “unmethylation” were used wrongly with each other.

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Fujimoto, M., Nakamura, Y., Iwaki, T. et al. Angelman syndrome with mosaic paternal uniparental disomy suggestive of mitotic nondisjunction. J Hum Genet 68, 87–90 (2023). https://doi.org/10.1038/s10038-022-01088-z

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