Monogenic hearing loss
Gene: SLC17A8Comment on list classification: Upgrading from red to green based on new evidence added.Created: 12 Jun 2019, 11:23 a.m.
Associated with Deafness, autosomal dominant 25 (#605583) in OMIM.
PMID: 18674745 - Ruel et al 2008 - 2 families with autosomal dominant nonsyndromic deafness and a missense mutation (p.A211V)
PMID: 24082139 - Gonzalez-Garay et al 2013 - 81 nonrelated volunteers underwent exome sequencing. Every nonsynonymous coding variant was interrogated for human inherited disease mutations using the HGMD.
A volunteer (patient 3934 - see Table S1) with nonsyndromic deafness was found to have risk alleles in two genes associated with autosomal dominant deafness (MYH14 p.M161I, SLC17A8 p.R75C) and had a three-generation positive family history of deafness.
PMID: 23967202 - Miyagawa et al 2013 - missense mutation (p.A374S) in SLC17A8 in 4 confirmed alleles in 432 patient alleles. Patients had hearing loss. Autosomal dominant.
PMID: 26969326 - Sloan-Heggen et al 2016 - 1 patient with hearing loss with a heterozygous missense variant p.P54L.
PMID: 27610647 - Chen et al 2016 - no access to publication. The gene is not mentioned in the abstract.
PMID: 28314816 - Ramet et al 2017 - mouse model. The A211 alanine in human VGLUTs corresponds to position 224 in the mouse VGLUT3 sequence (A224). The VGLUT3 A224V/A224V mice present the same progressive loss of hearing reported in humans. NOTE: the mouse is homozygous for the variant.
PMID: 30245029 - Azaiez et al 2018 - Deafness Variation Database - list NM_139319:p.Ala374Ser in SLC17A8 as benign.
Summary: >3 cases, all missense variants, mouse model supports the role of this gene in the hearing loss phenotype.Created: 5 Jun 2019, 10:30 a.m.
8 DM mutations HGMD multiple publications. DFNA25 #605583
Ruel et al 2008 PMID 18674745
Gonzalez-Garay et al 2013 PMID 24082139
Miyagawa et al 2013 PMID 23967202
Sloan-Heggen et al 2016 PMID 26969326
Chen et al 2016 PMID 27610647
Ramet et al 2017 PMID 28314816
Azaiez et al 2018 PMID 30245029Created: 17 Feb 2019, 4:35 p.m.
Comment on list classification: Confirmed with the first reviewer that this should remain as red as less convincing evidence than established green genes.Created: 2 Mar 2016, 11:22 a.m.
Only 3 missense variants reported in humans (according to HGMD), including one at a frequency of ~0.5% (1 in 200) which is too high for a congenital dominant gene to cause profound/severe hearing loss. The function of the other two missense variants have not been assessed. The knockout mouse model suggests an autosomal recessive loss-of-function mechanism, but the human data suggest autosomal dominant inheritance. Affected individuals with DFNA25 associated hearing loss typically manifest a high-frequency, slowly progressive sensorineural hearing loss in the postlingual period (PMID 12925340).Created: 24 Feb 2016, 10:42 p.m.
Mode of inheritance
Unknown
Phenotypes
#605583:Deafness, autosomal dominant 25
Publications
Comment when marking as ready: Expert review and OMIM confirmedCreated: 29 Jan 2016, 4:19 p.m.
Gene: slc17a8 has been classified as Green List (High Evidence).
Publications for gene: SLC17A8 were set to PMID: 12151341; 18215623; 18674745; 19915548; 9323205
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Amber List (Moderate Evidence).
Publications for SLC17A8 were set to PMID: 12151341; 18215623; 18674745; 19915548; 9323205
This gene has been classified as Green List (High Evidence).
Model of inheritance for gene SLC17A8 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
SLC17A8 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert
Model of inheritance for gene SLC17A8 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
SLC17A8 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert
Model of inheritance for gene SLC17A8 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
SLC17A8 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert
Model of inheritance for gene SLC17A8 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
SLC17A8 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert
SLC17A8 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Illumina TruGenome Clinical Sequencing Services,UKGTN,Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,Expert