Challenges of secondary finding disclosure in genomic medicine in rare diseases: A nation-wide survey of Japanese facilities outsourcing comprehensive genetic testing
Challenges of secondary finding disclosure in genomic medicine in rare diseases: A nation-wide survey of Japanese facilities outsourcing comprehensive genetic testing
复制标题
罕见疾病基因组医学二次发现披露的挑战：对日本设施外包综合基因检测的全国范围调查
DOI：
10.1038/s10038-022-01084-3
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发表时间：
2022
影响因子：
3.5
通讯作者：
Kosugi Shinji
中科院分区：
文献类型：
--
作者：
Hiromoto Kana;Yamada Takahiro;Tsuchiya Mio;Kawame Hiroshi;Nanba Eiji;Goto Yuichi;Kosugi Shinji
全面的基因组分析可能会揭示二次发现(SFS)，包括最初目标之外的基因的致病变异。在日本，对罕见疾病的全面遗传分析通常作为研究进行。因此，顺丰信息披露的现状和困难仍不明朗。为取得资料，以便适当披露罕见疾病的自选基因测试，我们进行了一项调查，探讨外判全面基因测试的机构在临床实践中如何处理自选基因测试。有效率为66.7%(40/60)。在回应的机构中，55%的机构有披露具有临床实用价值的SFS的政策，并认为目标是具有高外显性的可操作的SFS。这些机构在确定披露目标(51%)和遗传咨询(38%)方面存在困难。提高遗传素养，建立监测系统，以及为未受影响的携带者提供医疗保险，通常被认为是解决这些困难的办法。对海外和日本披露SFS的意愿的比较显示，日本更不愿意披露SFS(可提起诉讼的SFS的比例为86%，不可提起诉讼的SFS的比例为62%，不可起诉的SFS的比例为16%)。难以确定披露目标的小组更有可能在与其他机构的会议上讨论这一问题，并提交指导方针。这表明，有困难的小组无法单独在自己的设施内做出决定，并寻求与其他设施合作。这些调查结果表明，有必要建立一个系统，允许在制定确定SFS的政策的设施和指南中与专家进行磋商。
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.