Case report: investigation of sudden unexpected death in the young using a molecular autopsy

Simple item page
dc.contributor.advisorHeathfield, Laura Jane
dc.contributor.authorToefy, Tasneem
dc.date.accessioned2026-07-16T11:08:07Z
dc.date.available2026-07-16T11:08:07Z
dc.date.issued2026
dc.date.updated2026-07-16T11:06:52Z
dc.description.abstractSudden unexpected death in the young (SUDY) refers to the abrupt death of individuals aged 1–50 years, often linked to cardiovascular, respiratory, metabolic, or infectious diseases. However, in some cases, no clear cause of death is identified during standard post-mortem examinations. Through a molecular autopsy, using massively parallel sequencing, this study aimed to identify genetic variants that may have contributed to the sudden demise of a 43-year-old female during a half-marathon in 2018. At the time, no cause of death was established, and DNA was retained at autopsy. Clinical exome sequencing was done using the Illumina TruSight One Panel and 11 773 genetic variants were identified. Using standard criteria, variants were filtered using BaseSpace Variant Interpreter and ten were prioritised for further evaluation. Pathogenicity was assessed, indicating one was benign, four were likely benign, four were variants of uncertain significance (VUS) and one was likely pathogenic (LP). Sanger sequencing confirmed the heterozygous VUS, which were all in cardiovascular-related genes, as well as the homozygous LP variant (CPS1 c.1030_1032delinsGCT (p.Thr344Ala)) linked to metabolic dysfunction. Consultation with a forensic pathologist revealed that three VUS (MYBPC3 (c.3224C>G (p.Thr1075Ser)), TMEM43 (c.982C>T (p.Arg328Trp)), and ANK2 (c.385-6C>T (splice site)) complimented pathology findings and may have explained death. However, histological cardiac tissue analysis and further clinical history are required to confirm these findings. Furthermore, the LP CPS1 variant may be poorly understood in terms of pathological relevance and overlooked as contributory to death. This study demonstrates the value of clinical exome sequencing in identifying genetic variants that may contribute to SUDY. The findings highlight the complexity of linking genetic variations to sudden death and underscore the need for further research into metabolic and cardiovascular genetic mutations. Integrating genetic, pathological, and clinical data is essential to improve the understanding, prevention, and forensic investigation of SUDY.
dc.identifier.apacitationToefy, T. (2026). <i>Case report: investigation of sudden unexpected death in the young using a molecular autopsy</i>. (). University of Cape Town ,Faculty of Health Sciences ,Division of Forensic Medicine and Toxicology. Retrieved from http://hdl.handle.net/11427/43583en_ZA
dc.identifier.chicagocitationToefy, Tasneem. <i>"Case report: investigation of sudden unexpected death in the young using a molecular autopsy."</i> ., University of Cape Town ,Faculty of Health Sciences ,Division of Forensic Medicine and Toxicology, 2026. http://hdl.handle.net/11427/43583en_ZA
dc.identifier.citationToefy, T. 2026. Case report: investigation of sudden unexpected death in the young using a molecular autopsy. . University of Cape Town ,Faculty of Health Sciences ,Division of Forensic Medicine and Toxicology. http://hdl.handle.net/11427/43583en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Toefy, Tasneem AB - Sudden unexpected death in the young (SUDY) refers to the abrupt death of individuals aged 1–50 years, often linked to cardiovascular, respiratory, metabolic, or infectious diseases. However, in some cases, no clear cause of death is identified during standard post-mortem examinations. Through a molecular autopsy, using massively parallel sequencing, this study aimed to identify genetic variants that may have contributed to the sudden demise of a 43-year-old female during a half-marathon in 2018. At the time, no cause of death was established, and DNA was retained at autopsy. Clinical exome sequencing was done using the Illumina TruSight One Panel and 11 773 genetic variants were identified. Using standard criteria, variants were filtered using BaseSpace Variant Interpreter and ten were prioritised for further evaluation. Pathogenicity was assessed, indicating one was benign, four were likely benign, four were variants of uncertain significance (VUS) and one was likely pathogenic (LP). Sanger sequencing confirmed the heterozygous VUS, which were all in cardiovascular-related genes, as well as the homozygous LP variant (CPS1 c.1030_1032delinsGCT (p.Thr344Ala)) linked to metabolic dysfunction. Consultation with a forensic pathologist revealed that three VUS (MYBPC3 (c.3224C>G (p.Thr1075Ser)), TMEM43 (c.982C>T (p.Arg328Trp)), and ANK2 (c.385-6C>T (splice site)) complimented pathology findings and may have explained death. However, histological cardiac tissue analysis and further clinical history are required to confirm these findings. Furthermore, the LP CPS1 variant may be poorly understood in terms of pathological relevance and overlooked as contributory to death. This study demonstrates the value of clinical exome sequencing in identifying genetic variants that may contribute to SUDY. The findings highlight the complexity of linking genetic variations to sudden death and underscore the need for further research into metabolic and cardiovascular genetic mutations. Integrating genetic, pathological, and clinical data is essential to improve the understanding, prevention, and forensic investigation of SUDY. DA - 2026 DB - OpenUCT DP - University of Cape Town KW - sudden unexpected death in the young (SUDY) KW - post-mortem LK - https://open.uct.ac.za PB - University of Cape Town PY - 2026 T1 - Case report: investigation of sudden unexpected death in the young using a molecular autopsy TI - Case report: investigation of sudden unexpected death in the young using a molecular autopsy UR - http://hdl.handle.net/11427/43583 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/43583
dc.identifier.vancouvercitationToefy T. Case report: investigation of sudden unexpected death in the young using a molecular autopsy. []. University of Cape Town ,Faculty of Health Sciences ,Division of Forensic Medicine and Toxicology, 2026 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/43583en_ZA
dc.language.isoen
dc.language.rfc3066eng
dc.publisher.departmentDivision of Forensic Medicine and Toxicology
dc.publisher.facultyFaculty of Health Sciences
dc.publisher.institutionUniversity of Cape Town
dc.subjectsudden unexpected death in the young (SUDY)
dc.subjectpost-mortem
dc.titleCase report: investigation of sudden unexpected death in the young using a molecular autopsy
dc.typeThesis / Dissertation
dc.type.qualificationlevelMasters
dc.type.qualificationlevelMPhil
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
thesis_hsf_2026_toefy tasneem.pdf
Size:
1.53 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.72 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Masters