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Pediatrics - Cardiology

Houston, Texas

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Pediatrics - Cardiology
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SCN1B Mutation Analysis

SCN1B proteins (β1 and β1B) are the β1-subunits of the cardiac sodium channel conducting the INa current. The SCN1B gene spans 9.8-kb genomic distance at chromosome 19q13.1 and is composed of 6 exons. It is translated into two isoforms: β1, which is a 218-amino acid protein, and β1B, which is a 268-amino acid protein. Each of the two isoforms consists of a large extracellular N-terminal domain, a single transmembrane segment, and an intracellular C-terminal domain. Both the β1 and β1B transcripts are expressed in the heart and are abundant in Purkinje fibers that play a critical role in electric pulse conduction in heart. Previous studies have shown that functions of SCN1B include an increase in sodium channel expression at the cell surface, modulation of channel gating and voltage dependence, and a role in cell adhesion and recruitment of cytosolic proteins such as ankyrin-G. Mutations in SCN1B have been associated with cardiac conduction defect and Brugada syndrome type 5, which is a cardiac disorder characterized by typical ECG alterations, and is associated with a high risk for sudden cardiac death, affecting young subjects with structurally normal hearts. Definitive genotype/phenotype correlations have not been described.

The John Welsh Cardiovascular Diagnostic Laboratory offers molecular genetic testing for SCN1B mutations. Individuals are tested by automatic fluorescent DNA sequencing of the coding exons of the SCN1B gene. We strongly recommend initial testing of a clearly affected individual, if available, in order to provide the greatest test sensitivity and clearest interpretation of results for subsequent family members. Genetic counseling is recommended for all individuals.

Reasons for Referral

Molecular confirmation of the diagnosis of Brugada syndrome type 5 and cardiac conduction defect.

Methodology

Genomic DNA is analyzed for SCN1B mutations by automatic fluorescent DNA sequencing of the coding exons of the SCN1B gene, as well as the exon/intron junctions and a portion of the 5' and 3' untranslated region. Patient DNA is sequenced in both the forward and reverse orientations. If a mutation is identified, additional family members are analyzed only for the familial mutation by automatic fluorescent DNA sequencing.

Service Fees

Service Direct and Institutional Billing CPT Codes
Index Case (Full Gene) $750 per sample 81404, G0452
Additional Family Members $300 per sample; known familial mutation only 81403, G0452

Sensitivity

DNA Sequencing Analysis: Approximately 99 percent detection of mutations in coding exons 1-6 of SCN1B.

Specimen Requirements

Blood (preferred): EDTA (purple-top) tubes: Adult: 5 cc, Child: 5 cc, Infant: 2-3 cc
Tissue: Frozen (preferred), RNAlater, Formalin-fixed, Paraffin-embedded
Other Body Fluids: Call to inquire
Buccal Swabs: One swab from each cheek

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