Feasibility of analysis of the SCN5A gene in paraffin embedded samples in sudden infant death cases at the Pretoria Medico-Legal Laboratory, South Africa
| Autor: | Chantal van Niekerk, Lorraine du Toit-Prinsloo, Barbara Ströh van Deventer |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
Heterozygote medicine.medical_specialty 030204 cardiovascular system & hematology Real-Time Polymerase Chain Reaction Genetic analysis Sudden death High Resolution Melt NAV1.5 Voltage-Gated Sodium Channel Pathology and Forensic Medicine South Africa 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Clinical significance 030216 legal & forensic medicine Retrospective Studies Genetic testing Cause of death Paraffin Embedding medicine.diagnostic_test business.industry Myocardium Infant Newborn Infant Arrhythmias Cardiac Retrospective cohort study DNA Sequence Analysis DNA General Medicine Case-Control Studies Mutation Feasibility Studies Population study Female business Sudden Infant Death |
| Zdroj: | Forensic Science, Medicine and Pathology. 14:276-284 |
| ISSN: | 1556-2891 1547-769X |
| DOI: | 10.1007/s12024-018-9995-5 |
| Popis: | To determine variations in the SCN5A gene linked to inherited cardiac arrhythmogenic disorders in sudden, unexplained infant death (SUID) cases examined at the Pretoria Medico-Legal Laboratory, South Africa. A retrospective study was conducted on SUID cases and controls, analyzing DNA extracted from archived formalin-fixed, paraffin-embedded (FFPE) myocardial tissue samples as well as blood samples. A total of 48 FFPE tissue samples (cases), 10 control FFPE tissue samples and nine control blood samples were included. DNA extracted from all samples was used to test for variations in the SCN5A gene by using high resolution melt (HRM) real-time PCR and sequencing. Genetic analysis showed 31 different single nucleotide variants in the entire study population (n = 67). Five previously reported variants of known pathogenic significance, and 14 variants of benign clinical significance, were identified. The study found 12 different variants in the cases that were not published in any database or literature and were considered novel. Of these novel variants, two were predicted as "probably damaging" with a high level of certainty (found in four case samples), one (identified in another case sample) was predicted to be "possibly damaging" with a 50% chance of being disease-causing, and nine were predicted to be benign. This study shows the significant added value of using genetic testing in determining the cause of death in South African SUID cases. Considering the high heritability of these arrhythmic disorders, post mortem genetic testing could play an important role in the understanding of the pathogenesis thereof and could also aid in the diagnosis and treatment of family members at risk, ultimately preventing similar future cases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink