Abstract
Trio-based genome sequencing (GS) is useful for genetic analysis of cases in which exome sequencing failed to resolve the disease-causing variants. In this paper, we report two unrelated families with pathogenic deletions (one outside exome-covering genomic regions and the other involving a single exon) successfully identified by GS. Notably, mosaic deletions were found in both families, which were carefully evaluated in detail by analyzing GS data using Integrative Genomics Viewer, breakpoint PCR, quantitative PCR, and digital PCR. This study emphasizes the benefit of trio-based GS, enabling straightforward interpretation, further aided by other confirmatory experimental methods.
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Data availability
The data of this study are not publicly available due to concerns to maintain patient anonymity. Requests to access the data should be directed to the corresponding author. Only anonymized data are available to researchers upon request.
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Acknowledgements
We would like to thank the patients and their families for their participation in this study. We are also grateful to Ms. Sayaka Sugimoto, Ms. Mai Sato, Ms. Nobuko Watanabe, Ms. Kaori Takabe, and Mr. Takafumi Miyama at the Department of Human Genetics, Yokohama City University Graduate School of Medicine, for their excellent technical assistance. Genome analysis of these cases was supported by AMED project Study of whole-genome sequencing for the improvement of genomic medicine for rare diseases (PI: Norihiro Kokudo). During the preparation of this work the authors used the ChatGPT (https://chatgpt.com) in order to enhance the quality of English prose. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. Finally, we thank Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.
Funding
This work was supported by the Japan Agency for Medical Research and Development (AMED) under grant numbers JP24ek0109674, JP24ek0109760, JP24ek0109617, JP24ek0109648, and JP24ek0109677 (N. Matsumoto); Japan Society for the Promotion of Science (JSPS) KAKENHI under grant numbers JP23K15353 (N. Tsuchida), JP23K07229 (Y. Uchiyama), JP22K15646 (K. Hamanaka), JP21K07869 (E. Koshimizu), JP22K15901 (A. Fujita), JP23K27520 (S. Miyatake), JP23K27568 and JP23K18278 (T. Mizuguchi), and JP24K02230 (N. Matsumoto); and the Takeda Science Foundation (T. Mizuguchi, N. Matsumoto).
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Tsuchida, N., Uchiyama, Y., Hamanaka, K. et al. Mosaic deletions detected by genome sequencing in two families. J Hum Genet 70, 307–312 (2025). https://doi.org/10.1038/s10038-025-01336-y
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DOI: https://doi.org/10.1038/s10038-025-01336-y
