Kraatari-Tiri M, Haanpää MK, Willberg T, Pohjola P, Keski-Filppula R, Kuismin O, Moilanen JS, Häkli S, Rahikkala E. Clinical and Genetic Characteristics of Finnish Patients with Autosomal Recessive and Dominant Non-Syndromic Hearing Loss Due to Pathogenic TMC1 Variants. Journal of Clinical Medicine. 2022; 11(7):1837. https://doi.org/10.3390/jcm11071837
Clinical and genetic characteristics of Finnish patients with autosomal recessive and dominant non-syndromic hearing loss due to pathogenic TMC1 variants
|Author:||Kraatari-Tiri, Minna1,2; Haanpää, Maria K.3,4; Willberg, Tytti5;|
1Department of Clinical Genetics, Oulu University Hospital, 90029 Oulu, Finland
2PEDEGO Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, 90014 Oulu, Finland
3Department of Clinical Genetics, Turku University Hospital, 20521 Turku, Finland
4Department of Genomics, Turku University Hospital, 20521 Turku, Finland
5Department of Otorhinolaryngology, Turku University Hospital, 20521 Turku, Finland
6Department of Otorhinolaryngology, Oulu University Hospital, 90029 Oulu, Finland
|Online Access:||PDF Full Text (PDF, 0.9 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2022091559163
Multidisciplinary Digital Publishing Institute,
|Publish Date:|| 2022-09-15
Sensorineural hearing loss (SNHL) is one of the most common sensory deficits worldwide, and genetic factors contribute to at least 50–60% of the congenital hearing loss cases. The transmembrane channel-like protein 1 (TMC1) gene has been linked to autosomal recessive (DFNB7/11) and autosomal dominant (DFNA36) non-syndromic hearing loss, and it is a relatively common genetic cause of SNHL. Here, we report eight Finnish families with 11 affected family members with either recessively inherited homozygous or compound heterozygous TMC1 variants associated with congenital moderate-to-profound hearing loss, or a dominantly inherited heterozygous TMC1 variant associated with postlingual progressive hearing loss. We show that the TMC1 c.1534C>T, p.(Arg512*) variant is likely a founder variant that is enriched in the Finnish population. We describe a novel recessive disease-causing TMC1 c.968A>G, p.(Tyr323Cys) variant. We also show that individuals in this cohort who were diagnosed early and received timely hearing rehabilitation with hearing aids and cochlear implants (CI) have reached good speech perception in noise. Comparison of the genetic data with the outcome of CI rehabilitation increases our understanding of the extent to which underlying pathogenic gene variants explain the differences in CI rehabilitation outcomes.
Journal of clinical medicine
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3125 Otorhinolaryngology, ophthalmology
This study was funded by Academy of Finland (grant number 338446), Uolevi Mäki Foundation, and the Competitive State Research Financing of the Expert Responsibility Area of Oulu University Hospital (grant number VTR K36733).
|Academy of Finland Grant Number:||
338446 (Academy of Finland Funding decision)
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).