Monogenic hearing loss
Gene: KCNQ4Updating the mode of inheritance from monoallelic to 'both', after feedback from an Expert Reviewer who has another case in their lab. Feedback also included that the mice model with a homozygous 'dominant negative' mutation are also affected by progressive deafness (PMID:16437162).Created: 11 Oct 2018, 2:16 p.m.
PMID: 26036578 - a report of a family, where the proband had severe congenital/early onset hearing loss and was homozygous for a novel frameshift variant (8 nucleotide deletion resulting in a frameshift). KCNQ4 was also sequences in two of her sisters. One sister was heterozygous for the same variant but unaffected, the other was homozygous wild type. GJB2 and CDH23 were also examined. The parents and other siblings were not genotyped. The mechanism of the variant in homozygous form was suggested to result in complete loss of the A-domain and B-segment of the protein, causing loss of function due to failure of tetramer formation and CaM binding, whereas in heterozygous form, it was suggsted there may be sufficient tetramer formation and CaM binding sites to allow for a normal penotype. No functional studies were carried to confirm this hypothesis. There does not seem to be enough evidence at this time to change the mode of inheritance to 'both'.Created: 14 Aug 2018, 8:19 a.m.
New review confirms gene status and mode of inheritance; no changes required.Created: 1 Jun 2018, 3:10 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
#600101:Deafness, autosomal dominant 2A[Deafness, postlingualLoss of high frequencies at onsetLoss of mid- and low-frequencies laterTinnitus (variable)No vestibular impairment]
Comment when marking as ready: Expert review and OMIM confirmedCreated: 29 Jan 2016, 3:41 p.m.
Phenotypes for gene: KCNQ4 were changed from #600101:Deafness, autosomal dominant 2A to Deafness, autosomal dominant 2A, OMIM:600101
Tag watchlist was removed from gene: KCNQ4.
Publications for gene: KCNQ4 were set to 26036578; 10025409; 10080176; 10369879; 10571947; 10760249; 10760300; 10925378; 11450843; 12112653; 12670425; 16596322; 18030493; 20966080; 8035838; 9126484
Source Expert was removed from KCNQ4. Mode of inheritance for gene KCNQ4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Tag watchlist tag was added to gene: KCNQ4.
Publications for gene: KCNQ4 were set to 26036578; 10025409; 10080176; 10369879; 10571947; 10760249; 10760300; 10925378; 11450843; 12112653; 12670425; 16596322; 18030493; 20966080; 8035838; 9126484
Publications for gene: KCNQ4 were set to PMID:10025409; 10080176; 10369879; 10571947; 10760249; 10760300; 10925378; 11450843; 12112653; 12670425; 16596322; 18030493; 20966080; 8035838; 9126484
Phenotypes for KCNQ4 were set to #600101:Deafness, autosomal dominant 2A
Publications for KCNQ4 were set to PMID:10025409; 10080176; 10369879; 10571947; 10760249; 10760300; 10925378; 11450843; 12112653; 12670425; 16596322; 18030493; 20966080; 8035838; 9126484
Mode of inheritance for KCNQ4 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
This gene has been classified as Green List (High Evidence).
KCNQ4 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Emory Genetics Laboratory,UKGTN,Radboud University Medical Center, Nijmegen,Expert
KCNQ4 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Emory Genetics Laboratory,UKGTN,Radboud University Medical Center, Nijmegen,Expert
KCNQ4 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Emory Genetics Laboratory,UKGTN,Radboud University Medical Center, Nijmegen,Expert
KCNQ4 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Emory Genetics Laboratory,UKGTN,Radboud University Medical Center, Nijmegen,Expert