Genetic analysis in post-mortem samples with micro-ischemic alterations.

Forensic Sci Int

Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain; Medical Science Department, School of Medicine, University of Girona, Girona, Spain; Cardiology Service, Hospital Josep Trueta, Girona, Spain. Electronic address:

Published: February 2017

AI Article Synopsis

  • * A study of 56 autopsy samples revealed that myocardial infarction was the cause of death, and several rare genetic variations were identified, with some variants previously linked to heart conditions and one classified as harmful.
  • * The findings showed about 10% of variants were unique, but their clinical significance is unclear without further family studies, highlighting the need for larger research to understand genetic factors in patients with microscopic heart damage.

Article Abstract

Sudden cardiac arrest is a leading cause of death worldwide. Most cardiac arrests happen in patients who have previously suffered a myocardial infarct. The risk of sudden death after infarction may increase in people who carry a pathogenic genetic alteration in cardiac ion channels. We hypothesized that micro-ischemia could trigger lethal arrhythmogenesis, thus we sought to identify genetic alterations in cardiac ion channels in patients with micro-ischemic disease. We studied a cohort of 56 post-mortem samples. Autopsy studies identified myocardial infarction as the cause of death in each case. We used both Sanger sequencing and next-generation sequencing to screen candidate genes associated with sudden cardiac death. We identified six rare missense genetic variations in five unrelated patients. Two variants have been previously reported; one is associated with atrial fibrillation (SCN5A_p.H445D), and the other is predicted to be benign (ANK2_p.T2059M). The novel variants were predicted in silico as benign, except for one (RyR2_p.M4019T), which was classified as deleterious. Our post-mortem, micro-infarction cohort displayed a rate of nearly 10% non-common genetic variants. However, the clinical significance of most of the identified variants remains unknown due to lack of family assessment. Further analyses should be performed in large cohorts to clarify the role of ion-channel gene analysis in samples showing microscopic ischemic alterations.

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Source
http://dx.doi.org/10.1016/j.forsciint.2016.12.035DOI Listing

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