Analysis of TMIE gene mutations including the first large deletion of exon 1 with autosomal recessive non-syndromic deafness
Abstract Background Transmembrane inner ear (TMIE) protein is an essential component of the mechanotransduction complex. In collaboration with other components, TMIE aids the maintenance and function of the sensory hair cells. Autosomal recessive deafness-6 (DFNB6) is caused by mutated TMIE, a gene...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-022-01287-9 |
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| author | Sima Rayat Mohammad Farhadi Hessamaldin Emamdjomeh Saeid Morovvati Masoumeh Falah |
| author_facet | Sima Rayat Mohammad Farhadi Hessamaldin Emamdjomeh Saeid Morovvati Masoumeh Falah |
| author_sort | Sima Rayat |
| collection | DOAJ |
| description | Abstract Background Transmembrane inner ear (TMIE) protein is an essential component of the mechanotransduction complex. In collaboration with other components, TMIE aids the maintenance and function of the sensory hair cells. Autosomal recessive deafness-6 (DFNB6) is caused by mutated TMIE, a gene in the high genetic heterogeneity spectrum of deafness. Hearing loss has a significant impact on the global economy and the quality of life of affected persons, their families, and society. Here, three unrelated families with TMIE variants are presented. All three cases were found while studying the genetic causes of an Iranian cohort of subjects with cochlear implants. Methods Whole exome sequencing was performed to find possible genetic etiology in probands of families after a comprehensive medical evaluation for hearing loss. Co-segregation analysis in probands and other family members was performed by Sanger sequencing. The variants were interpreted per the American College of Medical Genetics and Genomics guidelines. Results Three different variants associated with TMIE were confirmed as reasons for autosomal recessive non-syndromic deafness. The first novel ~ 10-kb deletion surrounding exon 1 of TMIE along with two previously reported variants co-segregated with families including a frameshift variant c.122_125dup (p.Pro43fs) and a missense variant c.250 C > T; p.(Arg84Trp) in exons 2, and 3, respectively. Conclusion This study increases the mutational spectrum of the TMIE gene and highlights the importance of the large deletion of this gene as a reason for hearing loss. Moreover, an efficient and simple multiplex PCR assay was developed to determine the exact breakpoints of the TMIE deletion. |
| first_indexed | 2024-12-12T03:55:37Z |
| format | Article |
| id | doaj.art-e92d8271d23e48c3aef2735fd677ac22 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-12-12T03:55:37Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-e92d8271d23e48c3aef2735fd677ac222022-12-22T00:39:15ZengBMCBMC Medical Genomics1755-87942022-06-0115111010.1186/s12920-022-01287-9Analysis of TMIE gene mutations including the first large deletion of exon 1 with autosomal recessive non-syndromic deafnessSima Rayat0Mohammad Farhadi1Hessamaldin Emamdjomeh2Saeid Morovvati3Masoumeh Falah4ENT and Head and Neck Research Center, The Five Senses Health Institute, School of Medicine, Iran University of Medical SciencesENT and Head and Neck Research Center, The Five Senses Health Institute, School of Medicine, Iran University of Medical SciencesENT and Head and Neck Research Center, The Five Senses Health Institute, School of Medicine, Iran University of Medical SciencesDepartment of Genetics, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad UniversityENT and Head and Neck Research Center, The Five Senses Health Institute, School of Medicine, Iran University of Medical SciencesAbstract Background Transmembrane inner ear (TMIE) protein is an essential component of the mechanotransduction complex. In collaboration with other components, TMIE aids the maintenance and function of the sensory hair cells. Autosomal recessive deafness-6 (DFNB6) is caused by mutated TMIE, a gene in the high genetic heterogeneity spectrum of deafness. Hearing loss has a significant impact on the global economy and the quality of life of affected persons, their families, and society. Here, three unrelated families with TMIE variants are presented. All three cases were found while studying the genetic causes of an Iranian cohort of subjects with cochlear implants. Methods Whole exome sequencing was performed to find possible genetic etiology in probands of families after a comprehensive medical evaluation for hearing loss. Co-segregation analysis in probands and other family members was performed by Sanger sequencing. The variants were interpreted per the American College of Medical Genetics and Genomics guidelines. Results Three different variants associated with TMIE were confirmed as reasons for autosomal recessive non-syndromic deafness. The first novel ~ 10-kb deletion surrounding exon 1 of TMIE along with two previously reported variants co-segregated with families including a frameshift variant c.122_125dup (p.Pro43fs) and a missense variant c.250 C > T; p.(Arg84Trp) in exons 2, and 3, respectively. Conclusion This study increases the mutational spectrum of the TMIE gene and highlights the importance of the large deletion of this gene as a reason for hearing loss. Moreover, an efficient and simple multiplex PCR assay was developed to determine the exact breakpoints of the TMIE deletion.https://doi.org/10.1186/s12920-022-01287-9Hearing lossDFNB6TMIEWhole-exome sequencingCNV |
| spellingShingle | Sima Rayat Mohammad Farhadi Hessamaldin Emamdjomeh Saeid Morovvati Masoumeh Falah Analysis of TMIE gene mutations including the first large deletion of exon 1 with autosomal recessive non-syndromic deafness BMC Medical Genomics Hearing loss DFNB6 TMIE Whole-exome sequencing CNV |
| title | Analysis of TMIE gene mutations including the first large deletion of exon 1 with autosomal recessive non-syndromic deafness |
| title_full | Analysis of TMIE gene mutations including the first large deletion of exon 1 with autosomal recessive non-syndromic deafness |
| title_fullStr | Analysis of TMIE gene mutations including the first large deletion of exon 1 with autosomal recessive non-syndromic deafness |
| title_full_unstemmed | Analysis of TMIE gene mutations including the first large deletion of exon 1 with autosomal recessive non-syndromic deafness |
| title_short | Analysis of TMIE gene mutations including the first large deletion of exon 1 with autosomal recessive non-syndromic deafness |
| title_sort | analysis of tmie gene mutations including the first large deletion of exon 1 with autosomal recessive non syndromic deafness |
| topic | Hearing loss DFNB6 TMIE Whole-exome sequencing CNV |
| url | https://doi.org/10.1186/s12920-022-01287-9 |
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