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Pediatrics - Cardiology

Houston, Texas

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Pediatrics - Cardiology
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HCN4 Mutation Analysis

HCN4 gene contains eight exons spanning 49 kb of genomic distance that has been mapped to chromosome 15q24.1. The protein encoded by this gene is a member of the hyperpolarization-activated cyclic nucleotide-gated potassium channels. The encoded protein shows slow kinetics of activation and inactivation, and is necessary for the cardiac pacemaking process. This channel is activated by cAMP and may contribute to the native pacemaker currents in heart and in neurons. This channel may also mediate responses to sour stimuli. Two pseudogenes have been identified on chromosome 15. Mutations in this gene have been linked to sick sinus syndrome 2, also known as atrial fibrillation with bradyarrhythmia or familial sinus bradycardia and Brugada syndrome type 8 (BRS8). HCN4 mutations demonstrate autosomal dominant inheritance with a broad range of clinical severity both within and between families.

The John Welsh Cardiovascular Diagnostic Laboratory offers molecular genetic testing for HCN4 mutations. Individuals are tested by automatic fluorescent DNA sequencing of the coding exons of the HCN4 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 8 (BRS8) and sick sinus syndrome 2.

Methodology

Genomic DNA is analyzed for HCN4 mutations by automatic fluorescent DNA sequencing of the coding exons of the HCN4 gene, as well as the exon/intron junctions and a portion of the 5' and 3' untranslated regions. 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) $800 per sample 81405, 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 1-8 of HCN4.

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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