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Challenges of secondary finding disclosure in genomic medicine in rare diseases: A nation-wide survey of Japanese facilities outsourcing comprehensive genetic testing

Journal of Human Genetics volume 68, pages 1–9 (2023)Cite this article

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Abstract

Comprehensive genome analysis may reveal secondary findings (SFs) including pathogenic variants of genes other than those originally targeted. Comprehensive genetic analysis of rare diseases is generally performed as research in Japan. Therefore, the status and difficulties in SF disclosure remain unclear. To obtain information for the appropriate disclosure of SFs in rare diseases, we conducted a survey on how SFs are handled in clinical practice by facilities that outsource comprehensive genetic testing to other facilities. The response rate was 66.7% (40/60). Among the responding facilities, 55% had a policy of disclosing SFs with clinical utility and considered targeting actionable SFs with high penetrance. These facilities had difficulties in determining the disclosure targets (51%) and in genetic counseling (38%). Improving genetic literacy, establishment of surveillance systems, and providing insurance coverage for medical care to unaffected carriers were commonly cited as solutions to these difficulties. A comparison of the willingness to disclose SFs between overseas and in Japan showed more reluctance in Japan (86% vs. 65% for actionable SFs and 62% vs. 16% for non-actionable SFs). The group with difficulty in determining disclosure targets was significantly more likely to discuss this at conferences with other facilities and to refer guidelines. This suggests that the group with difficulties was unable to make decisions solely at their own facility and sought collaboration with other facilities. These findings suggest the necessity for a system that allows consultation with experts across facilities and guidelines that set forth policies for determining SFs.

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Fig. 1: Pathogenic variants considered for disclosure.
Fig. 2: Comparison of decision-making methods in facilities with and without difficulties in determining the target of disclosure.

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Acknowledgements

We would like to thank all the personnel at the institutions that returned the questionnaires. This study was supported by the Japan Ministry of Health, Labour and Welfare (grant numbers: 20AD1001).

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Authors and Affiliations

  1. Department of Genome Medical Center, Hyogo Prefectural Kobe Children’s Hospital, Hyogo, Japan

    Kana Hiromoto

  2. Department of Medical Ethics and Medical Genetics, Kyoto University School of Public Health, Kyoto, Japan

    Takahiro Yamada & Shinji Kosugi

  3. Amicus Therapeutics K.K., Tokyo, Japan

    Mio Tsuchiya

  4. Tohoku University Tohoku Medical Megabank Organization, Miyagi, Japan

    Hiroshi Kawame

  5. Department of Clinical Genetics, Jikei University, Tokyo, Japan

    Hiroshi Kawame

  6. Research Strategy Division, Organization for Research Initiative and Promotion, Tottori University, Tottori, Japan

    Eiji Nanba

  7. Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo, Japan

    Yuichi Goto

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Correspondence to Takahiro Yamada.

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Hiromoto, K., Yamada, T., Tsuchiya, M. et al. Challenges of secondary finding disclosure in genomic medicine in rare diseases: A nation-wide survey of Japanese facilities outsourcing comprehensive genetic testing. J Hum Genet 68, 1–9 (2023). https://doi.org/10.1038/s10038-022-01084-3

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