KCNQ1 Mutation Analysis
KCNQ1 gene, also known as KVLQT1, contains 16 exons and spans 400 kb of genomic DNA that was mapped to chromosome 11p15.5-p15.4. The protein encoded by this gene can form heteromultimers with two other proteins, KCNE1 and KCNE3 to make the voltage-gated potassium channel required for repolarization phase of the cardiac action potential. This gene exhibits tissue-specific imprinting, with preferential expression from the maternal allele in some tissues, and biallelic expression in others. This gene is located among other imprinted genes that are associated with Beckwith-Wiedemann syndrome (BWS) and itself has been shown to be disrupted by chromosomal rearrangements in patients with BWS. Alternatively spliced transcript variants have been found for this gene. KCNQ1 gene mutations are found in patients associated with familial atrial fibrillation 3, Jervell and Lange-Nielsen syndrome, long QT syndrome type 1 (LQT1) and short QT syndrome type 2 (SQT2). KCNQ1 mutations demonstrate autosomal dominant or recessive inheritance with a broad range of clinical severity both within and between families. Definitive genotype/phenotype correlations have not been described.
The John Welsh Cardiovascular Diagnostic Laboratory offers molecular genetic testing for KCNQ1 mutations. Individuals are tested by automatic fluorescent DNA sequencing of the coding exons of the KCNQ1 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 familial atrial fibrillation 3, Jervell and Lange-Nielsen syndrome, long QT syndrome type 1(LQT1), short QT syndrome type 2 (SQT2).
Genomic DNA is analyzed for KCNQ1 mutations by automatic fluorescent DNA sequencing of the coding exons of the KCNQ1 gene, as well as the exon/intron junctions and a portion of the 3' and 5' 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||Direct and Institutional Billing||CPT Codes|
|Index Case (Male or Female)||$1,000 per sample||81406, G0452|
|Additional Family Members||$300 per sample; known familial mutation only||81403, G0452|
DNA Sequencing Analysis: Approximately 99 percent detection of mutations in the coding exons 1-16 of KCNQ1.
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