Biallelic Mutations in the Otogelin‐Like Gene (OTOGL) Associated With Congenital Non‐Syndromic Sensorineural Hearing Loss in a Chinese Family
ABSTRACT Background Hearing loss, characterized by significant genetic heterogeneity, is a widespread global disorder. Mutations in the OTOG and OTOGL genes have recently been implicated in non‐syndromic sensorineural hearing loss. However, the mutation spectrum of OTOGL and its functional relevance...
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| Format: | Article |
| Language: | English |
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Wiley
2025-07-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.70122 |
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| author | Xiang Dai Jun Li Xijiang Hu Wenqian Cai |
| author_facet | Xiang Dai Jun Li Xijiang Hu Wenqian Cai |
| author_sort | Xiang Dai |
| collection | DOAJ |
| description | ABSTRACT Background Hearing loss, characterized by significant genetic heterogeneity, is a widespread global disorder. Mutations in the OTOG and OTOGL genes have recently been implicated in non‐syndromic sensorineural hearing loss. However, the mutation spectrum of OTOGL and its functional relevance remain incompletely understood. Methods We investigated a Chinese family with unexplained hearing loss using whole‐exome sequencing. Compound heterozygous mutations in the OTOGL gene were identified and validated through Sanger sequencing. The proband's clinical features were assessed through audiological evaluations, and genotype–phenotype correlation analysis was conducted. Additionally, single‐cell RNA sequencing analysis of the inner ear was performed to explore OTOGL's expression profile in auditory‐related cell types. Results Two compound heterozygous mutations in the OTOGL gene (p.Ile34Val and p.Phe319del) were identified in the proband, a 6‐year‐old boy with moderate congenital hearing loss. These mutations are predicted to be pathogenic and may explain the observed phenotype. Single‐cell RNA sequencing revealed specific OTOGL expression in key auditory‐related cell types, providing insights into its developmental and functional roles in the inner ear. Conclusion The findings have marked implications for molecular diagnosis and genetic counseling, potentially guiding more personalized treatment and intervention strategies in clinical practice. |
| format | Article |
| id | doaj-art-1e25451cc1d74246bb5259f93e8a343c |
| institution | DOAJ |
| issn | 2324-9269 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj-art-1e25451cc1d74246bb5259f93e8a343c2025-08-20T03:13:44ZengWileyMolecular Genetics & Genomic Medicine2324-92692025-07-01137n/an/a10.1002/mgg3.70122Biallelic Mutations in the Otogelin‐Like Gene (OTOGL) Associated With Congenital Non‐Syndromic Sensorineural Hearing Loss in a Chinese FamilyXiang Dai0Jun Li1Xijiang Hu2Wenqian Cai3Eugenic Genetics Laboratory Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology Wuhan ChinaDepartment of Otolaryngology Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology Wuhan ChinaEugenic Genetics Laboratory Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology Wuhan ChinaEugenic Genetics Laboratory Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology Wuhan ChinaABSTRACT Background Hearing loss, characterized by significant genetic heterogeneity, is a widespread global disorder. Mutations in the OTOG and OTOGL genes have recently been implicated in non‐syndromic sensorineural hearing loss. However, the mutation spectrum of OTOGL and its functional relevance remain incompletely understood. Methods We investigated a Chinese family with unexplained hearing loss using whole‐exome sequencing. Compound heterozygous mutations in the OTOGL gene were identified and validated through Sanger sequencing. The proband's clinical features were assessed through audiological evaluations, and genotype–phenotype correlation analysis was conducted. Additionally, single‐cell RNA sequencing analysis of the inner ear was performed to explore OTOGL's expression profile in auditory‐related cell types. Results Two compound heterozygous mutations in the OTOGL gene (p.Ile34Val and p.Phe319del) were identified in the proband, a 6‐year‐old boy with moderate congenital hearing loss. These mutations are predicted to be pathogenic and may explain the observed phenotype. Single‐cell RNA sequencing revealed specific OTOGL expression in key auditory‐related cell types, providing insights into its developmental and functional roles in the inner ear. Conclusion The findings have marked implications for molecular diagnosis and genetic counseling, potentially guiding more personalized treatment and intervention strategies in clinical practice.https://doi.org/10.1002/mgg3.70122mutationsnonsyndromic hearing lossOTOGLsingle‐cell RNA sequencingwhole exome sequencing |
| spellingShingle | Xiang Dai Jun Li Xijiang Hu Wenqian Cai Biallelic Mutations in the Otogelin‐Like Gene (OTOGL) Associated With Congenital Non‐Syndromic Sensorineural Hearing Loss in a Chinese Family Molecular Genetics & Genomic Medicine mutations nonsyndromic hearing loss OTOGL single‐cell RNA sequencing whole exome sequencing |
| title | Biallelic Mutations in the Otogelin‐Like Gene (OTOGL) Associated With Congenital Non‐Syndromic Sensorineural Hearing Loss in a Chinese Family |
| title_full | Biallelic Mutations in the Otogelin‐Like Gene (OTOGL) Associated With Congenital Non‐Syndromic Sensorineural Hearing Loss in a Chinese Family |
| title_fullStr | Biallelic Mutations in the Otogelin‐Like Gene (OTOGL) Associated With Congenital Non‐Syndromic Sensorineural Hearing Loss in a Chinese Family |
| title_full_unstemmed | Biallelic Mutations in the Otogelin‐Like Gene (OTOGL) Associated With Congenital Non‐Syndromic Sensorineural Hearing Loss in a Chinese Family |
| title_short | Biallelic Mutations in the Otogelin‐Like Gene (OTOGL) Associated With Congenital Non‐Syndromic Sensorineural Hearing Loss in a Chinese Family |
| title_sort | biallelic mutations in the otogelin like gene otogl associated with congenital non syndromic sensorineural hearing loss in a chinese family |
| topic | mutations nonsyndromic hearing loss OTOGL single‐cell RNA sequencing whole exome sequencing |
| url | https://doi.org/10.1002/mgg3.70122 |
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