RGD Reference Report - Association of TMTC2 With Human Nonsyndromic Sensorineural Hearing Loss. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Association of TMTC2 With Human Nonsyndromic Sensorineural Hearing Loss.

Authors: Runge, CL  Indap, A  Zhou, Y  Kent JW, JR  King, E  Erbe, CB  Cole, R  Littrell, J  Merath, K  James, R  Ruschendorf, F  Kerschner, JE  Marth, G  Hubner, N  Goring, HH  Friedland, DR  Kwok, WM  Olivier, M 
Citation: Runge CL, etal., JAMA Otolaryngol Head Neck Surg. 2016 Jun 16. doi: 10.1001/jamaoto.2016.1444.
RGD ID: 11252147
Pubmed: PMID:27311106   (View Abstract at PubMed)
PMCID: PMC5025373   (View Article at PubMed Central)
DOI: DOI:10.1001/jamaoto.2016.1444   (Journal Full-text)

Importance: Sensorineural hearing loss (SNHL) is commonly caused by conditions that affect cochlear structures or the auditory nerve, and the genes identified as causing SNHL to date only explain a fraction of the overall genetic risk for this debilitating disorder. It is likely that other genes and mutations also cause SNHL. Objective: To identify a candidate gene that causes bilateral, symmetric, progressive SNHL in a large multigeneration family of Northern European descent. Design, Setting, and Participants: In this prospective genotype and phenotype study performed from January 1, 2006, through April 1, 2016, a 6-generation family of Northern European descent with 19 individuals having reported early-onset hearing loss suggestive of an autosomal dominant inheritance were studied at a tertiary academic medical center. In addition, 179 unrelated adult individuals with SNHL and 186 adult individuals reporting nondeafness were examined. Main Outcomes and Measures: Sensorineural hearing loss. Results: Nine family members (5 women [55.6%]) provided clinical audiometric and medical records that documented hearing loss. The hearing loss is characterized as bilateral, symmetric, progressive SNHL that reached severe to profound loss in childhood. Audiometric configurations demonstrated a characteristic dip at 1000 to 2000 Hz. All affected family members wear hearing aids or have undergone cochlear implantation. Exome sequencing and linkage and association analyses identified a fully penetrant sequence variant (rs35725509) on chromosome 12q21 (logarithm of odds, 3.3) in the TMTC2 gene region that segregates with SNHL in this family. This gene explains the SNHL occurrence in this family. The variant is also associated with SNHL in a cohort of 363 unrelated individuals (179 patients with confirmed SNHL and 184 controls, P = 7 x 10-4). Conclusions and Relevance: A previously uncharacterized gene, TMTC2, has been identified as a candidate for causing progressive SNHL in humans. This finding identifies a novel locus that causes autosomal dominant SNHL and therefore a more detailed understanding of the genetic basis of SNHL. Because TMTC2 has not been previously reported to regulate auditory function, the discovery reveals a potentially new, uncharacterized mechanism of hearing loss.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Nonsyndromic Sensorineural Hearing Loss susceptibilityIAGP 11252147DNA:SNP:exon:rs35725509(human)RGD 
Nonsyndromic Sensorineural Hearing Loss susceptibilityISOTMTC2 (Homo sapiens)11252147; 11252147DNA:SNP:exon:rs35725509(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tmtc2  (transmembrane O-mannosyltransferase targeting cadherins 2)

Genes (Mus musculus)
Tmtc2  (transmembrane and tetratricopeptide repeat containing 2)

Genes (Homo sapiens)
TMTC2  (transmembrane O-mannosyltransferase targeting cadherins 2)


Additional Information