Structured postmortem genetic counselling and testing in sudden unexplained death among young adults in the Netherlands: results and implications regarding hereditary risk.

IF 1.8 Q4 GENETICS & HEREDITY

Journal of Community Genetics Pub Date : 2026-10-17 DOI:10.1007/s12687-026-00946-z

Tess M Wemeijer, Leonie A Verbaan, Wilma L J M Duijst, Yvonne M Hoedemaekers, Imke Christiaans

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引用次数: 0

Abstract

Introduction: Sudden unexplained death (SUD) in young adults may result from hereditary cardiovascular disorders that remain undetected even after conventional autopsy. Routine postmortem genetic testing may identify these disorders, improving determination of the cause of death while providing diagnostic and preventive opportunities for surviving blood relatives.

Methods: Between September 2022 and October 2025, 100 cases of SUD in young adults in the Netherlands were investigated using the NODOV (Nader Onderzoek naar de DoodsOorzaak bij (jong)Volwassenen) procedure. Genetic counselling was offered to surviving blood relatives in 50 cases where conventional autopsy findings suggested an inherited cardiovascular disorder. Conventional autopsy findings, medical history and family history guided phenotype-directed genetic testing using targeted gene panel analysis following whole-exome/genome sequencing.

Results: Genetic testing was successfully performed in 46 out of 50 cases and identified pathogenic variants in six cases involving the CACNA1C, BAG3, MYBPC3, LDL-R, KCNJ2, and PKD1 genes. Pretest genetic counselling proved important in guiding genetic testing in 10% of all cases and 50% of genetically confirmed cases. Pathogenic variants were identified in both structurally abnormal and autopsy-negative cases. Families received tailored genetic counselling and recommendations for clinical follow-up based on predictive genetic testing. Among the 44 families without a genetic diagnosis, 43 were advised to undergo clinical cardiovascular screening.

Conclusion: This study highlights the importance of a structured multidisciplinary postmortem investigation, such as the NODOV procedure, integrating pretest genetic counselling and tailored postmortem genetic testing. This approach may improve determination of cause of death (particularly in autopsy-negative cases), aid in the identification of hereditary cardiovascular disorders and facilitate preventive strategies for at-risk blood relatives.

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结构化的死后遗传咨询和检测在荷兰的年轻人中突然不明原因死亡：结果和影响遗传风险。

简介：年轻人的不明原因猝死（SUD）可能是由遗传性心血管疾病引起的，即使在常规尸检后也无法发现。常规的死后基因检测可以识别这些疾病，提高对死亡原因的确定，同时为幸存的血亲提供诊断和预防机会。方法：于2022年9月至2025年10月，采用NODOV （Nader Onderzoek naar de DoodsOorzaak bij (jong)Volwassenen）程序对荷兰100例年轻成人SUD进行调查。在50例常规尸检结果显示患有遗传性心血管疾病的病例中，向幸存的血亲提供了遗传咨询。采用全外显子组/基因组测序后的靶向基因面板分析，利用常规尸检结果、病史和家族史指导表型定向基因检测。结果：50例患者中有46例成功进行了基因检测，并在6例患者中发现了涉及CACNA1C、BAG3、MYBPC3、LDL-R、KCNJ2和PKD1基因的致病变异。在10%的病例和50%的基因确诊病例中，检测前遗传咨询证明对指导基因检测很重要。在结构异常和尸检阴性的病例中都发现了致病变异。家庭得到了量身定制的遗传咨询和基于预测性基因检测的临床随访建议。在44个没有基因诊断的家庭中，43个被建议进行临床心血管筛查。结论：本研究强调了结构化多学科死后调查的重要性，如NODOV程序，整合检测前遗传咨询和量身定制的死后基因检测。这种方法可以改善死因的确定（特别是在尸检阴性病例中），有助于确定遗传性心血管疾病，并促进高危血亲的预防战略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Community Genetics GENETICS & HEREDITY-

CiteScore

3.30

自引率

5.30%

发文量

期刊介绍： The Journal of Community Genetics is an international forum for research in the ever-expanding field of community genetics, the art and science of applying medical genetics to human communities for the benefit of their individuals. Community genetics comprises all activities which identify persons at increased genetic risk and has an interest in assessing this risk, in order to enable those at risk to make informed decisions. Community genetics services thus encompass such activities as genetic screening, registration of genetic conditions in the population, routine preconceptional and prenatal genetic consultations, public education on genetic issues, and public debate on related ethical issues. The Journal of Community Genetics has a multidisciplinary scope. It covers medical genetics, epidemiology, genetics in primary care, public health aspects of genetics, and ethical, legal, social and economic issues. Its intention is to serve as a forum for community genetics worldwide, with a focus on low- and middle-income countries. The journal features original research papers, reviews, short communications, program reports, news, and correspondence. Program reports describe illustrative projects in the field of community genetics, e.g., design and progress of an educational program or the protocol and achievement of a gene bank. Case reports describing individual patients are not accepted.