Clinical and Genetic Characteristics of Finnish Patients with Autosomal Recessive and Dominant Non-Syndromic Hearing Loss Due to Pathogenic <i>TMC1</i> Variants
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 (<i>TMC1</i>) gene has been linked to autosomal recessive (DFNB7/11) an...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
|
| Series: | Journal of Clinical Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0383/11/7/1837 |
| _version_ | 1797438805585690624 |
|---|---|
| author | Minna Kraatari-Tiri Maria K. Haanpää Tytti Willberg Pia Pohjola Riikka Keski-Filppula Outi Kuismin Jukka S. Moilanen Sanna Häkli Elisa Rahikkala |
| author_facet | Minna Kraatari-Tiri Maria K. Haanpää Tytti Willberg Pia Pohjola Riikka Keski-Filppula Outi Kuismin Jukka S. Moilanen Sanna Häkli Elisa Rahikkala |
| author_sort | Minna Kraatari-Tiri |
| collection | DOAJ |
| description | 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 (<i>TMC1</i>) 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 <i>TMC1</i> variants associated with congenital moderate-to-profound hearing loss, or a dominantly inherited heterozygous <i>TMC1</i> variant associated with postlingual progressive hearing loss. We show that the <i>TMC1</i> 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 <i>TMC1</i> 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. |
| first_indexed | 2024-03-09T11:43:36Z |
| format | Article |
| id | doaj.art-7cb5677262ea4623bb4f06d3872304fa |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T11:43:36Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-7cb5677262ea4623bb4f06d3872304fa2023-11-30T23:27:33ZengMDPI AGJournal of Clinical Medicine2077-03832022-03-01117183710.3390/jcm11071837Clinical and Genetic Characteristics of Finnish Patients with Autosomal Recessive and Dominant Non-Syndromic Hearing Loss Due to Pathogenic <i>TMC1</i> VariantsMinna Kraatari-Tiri0Maria K. Haanpää1Tytti Willberg2Pia Pohjola3Riikka Keski-Filppula4Outi Kuismin5Jukka S. Moilanen6Sanna Häkli7Elisa Rahikkala8Department of Clinical Genetics, Oulu University Hospital, 90029 Oulu, FinlandDepartment of Clinical Genetics, Turku University Hospital, 20521 Turku, FinlandDepartment of Otorhinolaryngology, Turku University Hospital, 20521 Turku, FinlandDepartment of Genomics, Turku University Hospital, 20521 Turku, FinlandDepartment of Clinical Genetics, Oulu University Hospital, 90029 Oulu, FinlandDepartment of Clinical Genetics, Oulu University Hospital, 90029 Oulu, FinlandDepartment of Clinical Genetics, Oulu University Hospital, 90029 Oulu, FinlandPEDEGO Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, 90014 Oulu, FinlandDepartment of Clinical Genetics, Oulu University Hospital, 90029 Oulu, FinlandSensorineural 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 (<i>TMC1</i>) 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 <i>TMC1</i> variants associated with congenital moderate-to-profound hearing loss, or a dominantly inherited heterozygous <i>TMC1</i> variant associated with postlingual progressive hearing loss. We show that the <i>TMC1</i> 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 <i>TMC1</i> 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.https://www.mdpi.com/2077-0383/11/7/1837<i>TMC1</i>hearing losscochlear implanthearing rehabilitationcongenital |
| spellingShingle | Minna Kraatari-Tiri Maria K. Haanpää Tytti Willberg Pia Pohjola Riikka Keski-Filppula Outi Kuismin Jukka S. Moilanen Sanna Häkli Elisa Rahikkala Clinical and Genetic Characteristics of Finnish Patients with Autosomal Recessive and Dominant Non-Syndromic Hearing Loss Due to Pathogenic <i>TMC1</i> Variants Journal of Clinical Medicine <i>TMC1</i> hearing loss cochlear implant hearing rehabilitation congenital |
| title | Clinical and Genetic Characteristics of Finnish Patients with Autosomal Recessive and Dominant Non-Syndromic Hearing Loss Due to Pathogenic <i>TMC1</i> Variants |
| title_full | Clinical and Genetic Characteristics of Finnish Patients with Autosomal Recessive and Dominant Non-Syndromic Hearing Loss Due to Pathogenic <i>TMC1</i> Variants |
| title_fullStr | Clinical and Genetic Characteristics of Finnish Patients with Autosomal Recessive and Dominant Non-Syndromic Hearing Loss Due to Pathogenic <i>TMC1</i> Variants |
| title_full_unstemmed | Clinical and Genetic Characteristics of Finnish Patients with Autosomal Recessive and Dominant Non-Syndromic Hearing Loss Due to Pathogenic <i>TMC1</i> Variants |
| title_short | Clinical and Genetic Characteristics of Finnish Patients with Autosomal Recessive and Dominant Non-Syndromic Hearing Loss Due to Pathogenic <i>TMC1</i> Variants |
| title_sort | clinical and genetic characteristics of finnish patients with autosomal recessive and dominant non syndromic hearing loss due to pathogenic i tmc1 i variants |
| topic | <i>TMC1</i> hearing loss cochlear implant hearing rehabilitation congenital |
| url | https://www.mdpi.com/2077-0383/11/7/1837 |
| work_keys_str_mv | AT minnakraataritiri clinicalandgeneticcharacteristicsoffinnishpatientswithautosomalrecessiveanddominantnonsyndromichearinglossduetopathogenicitmc1ivariants AT mariakhaanpaa clinicalandgeneticcharacteristicsoffinnishpatientswithautosomalrecessiveanddominantnonsyndromichearinglossduetopathogenicitmc1ivariants AT tyttiwillberg clinicalandgeneticcharacteristicsoffinnishpatientswithautosomalrecessiveanddominantnonsyndromichearinglossduetopathogenicitmc1ivariants AT piapohjola clinicalandgeneticcharacteristicsoffinnishpatientswithautosomalrecessiveanddominantnonsyndromichearinglossduetopathogenicitmc1ivariants AT riikkakeskifilppula clinicalandgeneticcharacteristicsoffinnishpatientswithautosomalrecessiveanddominantnonsyndromichearinglossduetopathogenicitmc1ivariants AT outikuismin clinicalandgeneticcharacteristicsoffinnishpatientswithautosomalrecessiveanddominantnonsyndromichearinglossduetopathogenicitmc1ivariants AT jukkasmoilanen clinicalandgeneticcharacteristicsoffinnishpatientswithautosomalrecessiveanddominantnonsyndromichearinglossduetopathogenicitmc1ivariants AT sannahakli clinicalandgeneticcharacteristicsoffinnishpatientswithautosomalrecessiveanddominantnonsyndromichearinglossduetopathogenicitmc1ivariants AT elisarahikkala clinicalandgeneticcharacteristicsoffinnishpatientswithautosomalrecessiveanddominantnonsyndromichearinglossduetopathogenicitmc1ivariants |