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Role of SCN5A coding and non-coding sequences in Brugada syndrome onset: What's behind the scenes?
- Source :
- Biomedical Journal, Biomedical Journal, Vol 42, Iss 4, Pp 252-260 (2019)
- Publication Year :
- 2018
-
Abstract
- Background: Brugada syndrome (BrS) is a rare inherited cardiac arrhythmia associated with a high risk of sudden cardiac death (SCD) due to ventricular fibrillation (VF). BrS is characterized by coved-type ST-segment elevation in the right precordial leads (V1-V3). Mutations in SCN5A gene coding for the α-subunit of the NaV1.5 cardiac sodium channel are identified in 15–30% of BrS cases. Genetic testing of BrS patients generally involves sequencing of the protein-coding portions and flanking intronic regions of SCN5A. This excludes the 5′UTR and 3′UTR from the routine genetic testing. Methods: We here screened the coding sequence, the flanking intronic regions as well as the 5′ and 3′UTR regions of SCN5A gene and further five candidate genes (GPD1L, SCN1B, KCNE3, SCN4B, and MOG1) in a Tunisian family diagnosed with BrS. Results: A new SCN5A-Q1000K mutation was identified along with two common polymorphisms (H558R and D1819). Multiple genetic variants were identified on the SCN5A 3′UTR, one of which is predicted to create additional microRNA binding site for miR-1270. Additionally, we identified the hsa-miR-219a-rs107822. No relevant coding sequence variant was identified in the remaining studied candidate genes. Conclusions: The absence of genotype-phenotype concordance within all the identified genetic variants in this family gives extra evidences about the complexity of the disease and suggests that the occurrence and prognosis of BrS is most likely controlled by a combination of multiple genetic factors, rather than a single variant. Most SCN5A variants were localized in non-coding regions hypothesizing an impact on the miRNA-target complementarities. Keywords: SCN5A, Brugada syndrome, 3′UTR, microRNAs, Genotype-phenotype correlation
- Subjects :
- 0301 basic medicine
Adult
Male
Candidate gene
congenital, hereditary, and neonatal diseases and abnormalities
Original article
Genotype-phenotype correlation
Genotype
Biology
3′UTR
medicine.disease_cause
Sudden cardiac death
NAV1.5 Voltage-Gated Sodium Channel
03 medical and health sciences
0302 clinical medicine
SCN1B
medicine
Coding region
Humans
Brugada syndrome
cardiovascular diseases
lcsh:QH301-705.5
SCN5A
Genetic testing
Aged
Genetics
Mutation
lcsh:R5-920
Polymorphism, Genetic
medicine.diagnostic_test
Cardiac arrhythmia
General Medicine
Middle Aged
medicine.disease
microRNAs
030104 developmental biology
Phenotype
lcsh:Biology (General)
Potassium Channels, Voltage-Gated
030220 oncology & carcinogenesis
cardiovascular system
Female
lcsh:Medicine (General)
Subjects
Details
- ISSN :
- 23202890
- Volume :
- 42
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Biomedical journal
- Accession number :
- edsair.doi.dedup.....0898052fd752e56ad02656445bd57d53