KCNE1 Mutation Analysis
KCNE1 (potassium voltage-gated channel, Isk-related family, member 1) gene encodes the KCNE1 protein, which regulates a channel composed of proteins produced by the KCNQ1 gene. Four alpha subunits, each made from the KCNQ1 gene, form the structure of each channel. One beta subunit (MinK), produced from the KCNE1 gene, binds to the channel and regulates its activity. These channels are active in the inner ear and in cardiac muscle, where they transport potassium ions out of cells, playing a role in maintaining the proper ion balance needed for normal hearing and in recharging the muscle after each contraction to maintain a regular heartbeat, repectively. KCNE1 gene contains one exon spanning 65.5 kb of genomic distance that was mapped to chromosome 21q22.12. Mutations in KCNE1 are responsible for long QT syndrome type 5 (LQT5). In its rare homozygous forms, it can lead to Jervell and Lange-Nielsen syndrome (JLNS, an autosomal recessive form of LQTS). KCNE1 mutations demonstrate autosomal dominant 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 KCNE1 mutations. Individuals are tested by automatic fluorescent DNA sequencing of the coding exons of the KCNE1 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 long QT syndrome type 5 (LQT5), Jervell and Lange-Nielsen syndrome (JLNS).
Genomic DNA is analyzed for KCNE1 mutations by automatic fluorescent DNA sequencing of the coding exons of the KCNE1 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||Direct and Institutional Billing||CPT Codes|
|Index Case (Full Gene)||$600 per sample||81403, G0452|
|Additional Family Members||$300 per sample; known familial mutation only||81403, G0452|
DNA Sequencing Analysis: Approximately 99 percent detection of mutations in coding exon of KCNE1.
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