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A harmful MYH11 variant detected in a family with thoracic aortic dissection and patent ductus arteriosus

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Abstract

Thoracic aortic dissection (TAD) is an important cause of sudden cardiac death and is characterized by high morbidity, mortality, and a poor prognosis. Patent ductus arteriosus (PDA) is a common congenital heart disease. The pathogenesis of both TAD and PDA has been reported to be related to genetic factors. The MYH11 gene, which encodes myosin heavy chain 11, has been reported in individuals with both TAD and PDA. Herein, we first detected a harmful MYH11 missense variant (c. T3728C, p. L1243P) in a TAD and PDA family. This missense variant co-segregated with the TAD/PDA phenotype in this family of four individuals, providing evidence of its harmfulness. Histopathological examinations revealed the presence of fragmented, broken, and lessened elastic fibers and the deposition of proteoglycans in the median of aortic dissection. Moreover, the immunofluorescence results showed that the labeled MYH11 protein in the tissue of the aortic dissection was weaker than that in the normal aorta. We present this familial case to stress the necessity of postmortem genetic testing in such cases among forensic practices. Identifying those culprit gene variants can direct effective genetic counseling and personalized health management in family members (especially first-degree relatives) with high-risk genotypes.

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Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (grant number: 82271923).

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Author notes

  1. Meichen Pan and Xiaoshan Tan contributed to the work equally.

Authors and Affiliations

  1. Department of Forensic Medicine, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Hankou, Wuhan, 430030, Hubei, China

    Meichen Pan, Xiaoshan Tan, Tianying Sun, Weiwei Zhu, Huine Liu, Qian Liu & Hongmei Dong

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  1. Meichen Pan
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  2. Xiaoshan Tan
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  4. Weiwei Zhu
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  7. Hongmei Dong
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Contributions

Conceptualization: Meichen Pan and Hongmei Dong; formal analysis and investigation: Xiaoshan Tan, Tianying Sun, Weiwei Zhu, and Huine Liu; writing—original draft preparation: Meichen Pan, Xiaoshan Tan; writing—review and editing: Meichen Pan, Xiaoshan Tan, and Hongmei Dong; supervision: Hongmei Dong.

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Correspondence to Hongmei Dong.

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All data and sample collections were handled in strict accordance with the ethical guidelines of the Tongji Medical College, Huazhong University of Science and Technology.

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Informed consent for publishing this scientific report was obtained from the husband of the deceased.

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Pan, M., Tan, X., Sun, T. et al. A harmful MYH11 variant detected in a family with thoracic aortic dissection and patent ductus arteriosus. Forensic Sci Med Pathol 20, 212–218 (2024). https://doi.org/10.1007/s12024-023-00650-1

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