Novel cis compound heterozygous variants in MYO6 causes early onset of non-syndromic hearing loss in a Chinese family
Background: Mutations in the MYO6 gene have been associated with both autosomal dominant non-syndromic hearing loss (ADNSHL) and autosomal recessive non-syndromic hearing loss (ARNSHL), with a cumulative identification of 125 pathogenic variants. To investigate the underlying genetic factor within a...
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1275633/full |
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| author | Haiting Ji Haiting Ji Haiting Ji Lichun Zhang Hafiz Muhammad Jafar Hussain Ayesha Aftab Huiqian Yu Huiqian Yu Huiqian Yu Min Xiao |
| author_facet | Haiting Ji Haiting Ji Haiting Ji Lichun Zhang Hafiz Muhammad Jafar Hussain Ayesha Aftab Huiqian Yu Huiqian Yu Huiqian Yu Min Xiao |
| author_sort | Haiting Ji |
| collection | DOAJ |
| description | Background: Mutations in the MYO6 gene have been associated with both autosomal dominant non-syndromic hearing loss (ADNSHL) and autosomal recessive non-syndromic hearing loss (ARNSHL), with a cumulative identification of 125 pathogenic variants. To investigate the underlying genetic factor within a Chinese family affected with heriditary hearing loss, prompted the utilization of high-throughput sequencing.Method: A detailed clinical investigation was performed. Genetic testing was performed by using target panel sequencing, and Sanger sequencing. Targeted sequencing identified the variants and Sanger sequencing was employed to validate segregation of the identified variants within family. Additionally, bioinformatics analysis was performed to strengthen our findings.Results: Clinical investigation revealed the family members were affected by progressive and sensorineural hearing loss with an onset around 8–10 years old. Furthermore, genetic testing identified novel MYO6 variants, c.[2377T>G; 2382G>T] p.[Trp793Gly; Lys794Asn], positioned in a cis pattern, as plausible pathogenic contributors to early-onset hearing loss characterized by a severe and progressive course. Moreover, bioinformatics analysis showd disruptin in hydrogen bonding of mutant amino acids with interactive amino acids.Conclusion: Our research uncovered a relationship between mutations in the MYO6 gene and non-syndromic hearing loss. We identified two variants, c.[2377T>G; 2382G>T] p.[Trp793Gly; Lys794Asn] in MYO6 as strong candidates responsible for the observed progressive hereditary hearing loss. This study not only adds to our knowledge about hearing problems related to MYO6 but also reveals the presence of monogenic compound heterozygosity. Our study will provide a new sight for genetic diagnosis in such patients and their management for future use. |
| first_indexed | 2024-03-08T14:48:24Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-08T14:48:24Z |
| publishDate | 2024-01-01 |
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| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-d4d7883cb1384b3eb5502209d0c79fcd2024-01-11T05:28:46ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-01-011410.3389/fgene.2023.12756331275633Novel cis compound heterozygous variants in MYO6 causes early onset of non-syndromic hearing loss in a Chinese familyHaiting Ji0Haiting Ji1Haiting Ji2Lichun Zhang3Hafiz Muhammad Jafar Hussain4Ayesha Aftab5Huiqian Yu6Huiqian Yu7Huiqian Yu8Min Xiao9Department of Otorhinolaryngology, Affiliated Eye and ENT Hospital of Fudan University, Shanghai, ChinaENT Institute and Otorhinolaryngology, Department of Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, ChinaNHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, ChinaDepartment of Otorhinolaryngology, Head and Neck Surgery, Otto Körner, Rostock University Medical Center, Rostock, GermanyMolecular and Human Genetics, Baylor College of Medicine, Houston, TX, United StatesDepartment of Biological Sciences, International Islamic University, Islamabad, PakistanDepartment of Otorhinolaryngology, Affiliated Eye and ENT Hospital of Fudan University, Shanghai, ChinaENT Institute and Otorhinolaryngology, Department of Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, ChinaNHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, ChinaShanghai Ji Ai Genetics and IVF Institute, The Obstetrics and Gynecology Hospital of Fudan University, Shanghai, ChinaBackground: Mutations in the MYO6 gene have been associated with both autosomal dominant non-syndromic hearing loss (ADNSHL) and autosomal recessive non-syndromic hearing loss (ARNSHL), with a cumulative identification of 125 pathogenic variants. To investigate the underlying genetic factor within a Chinese family affected with heriditary hearing loss, prompted the utilization of high-throughput sequencing.Method: A detailed clinical investigation was performed. Genetic testing was performed by using target panel sequencing, and Sanger sequencing. Targeted sequencing identified the variants and Sanger sequencing was employed to validate segregation of the identified variants within family. Additionally, bioinformatics analysis was performed to strengthen our findings.Results: Clinical investigation revealed the family members were affected by progressive and sensorineural hearing loss with an onset around 8–10 years old. Furthermore, genetic testing identified novel MYO6 variants, c.[2377T>G; 2382G>T] p.[Trp793Gly; Lys794Asn], positioned in a cis pattern, as plausible pathogenic contributors to early-onset hearing loss characterized by a severe and progressive course. Moreover, bioinformatics analysis showd disruptin in hydrogen bonding of mutant amino acids with interactive amino acids.Conclusion: Our research uncovered a relationship between mutations in the MYO6 gene and non-syndromic hearing loss. We identified two variants, c.[2377T>G; 2382G>T] p.[Trp793Gly; Lys794Asn] in MYO6 as strong candidates responsible for the observed progressive hereditary hearing loss. This study not only adds to our knowledge about hearing problems related to MYO6 but also reveals the presence of monogenic compound heterozygosity. Our study will provide a new sight for genetic diagnosis in such patients and their management for future use.https://www.frontiersin.org/articles/10.3389/fgene.2023.1275633/fullnon-syndromic hearing losstargeted gene panel sequencingSanger sequencingMYO6cis pattern |
| spellingShingle | Haiting Ji Haiting Ji Haiting Ji Lichun Zhang Hafiz Muhammad Jafar Hussain Ayesha Aftab Huiqian Yu Huiqian Yu Huiqian Yu Min Xiao Novel cis compound heterozygous variants in MYO6 causes early onset of non-syndromic hearing loss in a Chinese family Frontiers in Genetics non-syndromic hearing loss targeted gene panel sequencing Sanger sequencing MYO6 cis pattern |
| title | Novel cis compound heterozygous variants in MYO6 causes early onset of non-syndromic hearing loss in a Chinese family |
| title_full | Novel cis compound heterozygous variants in MYO6 causes early onset of non-syndromic hearing loss in a Chinese family |
| title_fullStr | Novel cis compound heterozygous variants in MYO6 causes early onset of non-syndromic hearing loss in a Chinese family |
| title_full_unstemmed | Novel cis compound heterozygous variants in MYO6 causes early onset of non-syndromic hearing loss in a Chinese family |
| title_short | Novel cis compound heterozygous variants in MYO6 causes early onset of non-syndromic hearing loss in a Chinese family |
| title_sort | novel cis compound heterozygous variants in myo6 causes early onset of non syndromic hearing loss in a chinese family |
| topic | non-syndromic hearing loss targeted gene panel sequencing Sanger sequencing MYO6 cis pattern |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1275633/full |
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