KCNQ4
The Clinical Diagnostics Service of the Molecular Otolaryngology Research Laboratory is a Joint Commission-approved CLIA-accredited diagnostic laboratory that offers mutation screening of several genes.

DFNA2 (OMIM#:  #600101)
Two genes are responsible for autosomal dominant nonsyndromic sensorineural hearing loss at the DNFA2 locus, KCNQ4 and GJB3. Both of these genes map to chromosome 1p34-p35.

KCNQ4 (OMIM#:  *603537)
KCNQ4 is voltage-gated potassium channel expressed in the outer hair cells of the cochlea.  The gene has 14 exons that encode a 695 amino acid protein.  Mutations in KCNQ4 are found persons with high-frequency, autosomal dominant, nonsyndromic sensorineural hearing loss.  At least eight different mutations in KCNQ4 have been identified in families segregating autosomal dominant nonsyndromic hearing loss.

MORL screening methodology
Screening for KCNQ4 is performed via DHPLC and sequencing.  Oligonucleotide primers have been designed to amplify each exon.  Amplified samples are run on the DHPLC; abnormal elution profiles are sequenced to identify specific mutations.  Exons carrying known SNPs are directly sequenced.

Sensitivity
Sensitivity is greater than 98%.

Turn-around time
Turn around time is approximately 3 months.

Cost: $525

Indications for screening
This test is appropriate for any patient with high frequency, nonsyndromic hearing impairment and a family history consistent with autosomal dominant inheritance.

GeneTests  GeneReviews – Deafness and Hereditary Hearing Loss

References
Coucke, P. J et al.:  Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families. Hum. Molec. Genet. 8: 1321-1328, 1999.
PubMed ID:  10369879
PubMed Search

Kamada, F. et al.:  A novel KCNQ4 one-base deletion in a large pedigree with hearing loss: implication for the genotype-phenotype correlation. J. Hum. Genet. 51: 455-460, 2006.
PubMed ID: 16596322
PubMed Search

Kharkovets, T et al.:  KCNQ4, a K(+) channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway. Proc. Nat. Acad. Sci. 97: 4333-4338, 2000.
PubMed ID: 10760300
PubMed Search

Kubisch, C. et al.:  KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell 96: 437-446, 1999.
PubMed ID: 10025409 
PubMed Search

Talebizadeh, Z. et al.:  Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss. Hum. Mutat. 14: 493-501, 1999.
PubMed ID: 10571947
PubMed Search

Trussell, L. et al.:  Mutant ion channel in cochlear hair cells causes deafness. Proc. Nat. Acad. Sci. 97: 3786-3788, 2000.
PubMed ID: 10760249
PubMed Search

Van Camp, G. et al.:  A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment. Hum. Mutat. 20: 15-19, 2002.
PubMed ID: 12112653
PubMed Search

Van Camp, G. et al.:  Linkage analysis of progressive hearing loss in five extended families maps the DFNA2 gene to a 1.25-Mb region on chromosome 1p. Genomics 41: 70-74, 1997.
PubMed ID: 9126484
PubMed Search

Van Hauwe, P. et al.:  Deafness linked to DFNA2: one locus but how many genes? (Letter)Nature Genet. 21: 263 only, 1999.
PubMed ID: 10080176
PubMed Search

Van Hauwe, P. et al.:  Mutations in the KCNQ4 K(+) channel gene, responsible for autosomal dominant hearing loss, cluster in the channel pore region. Am. J. Med. Genet. 93: 184-187, 2000.
PubMed ID: 10925378
PubMed Search