Next-generation sequencing improves precision medicine in hearing loss
Background: An early etiological diagnosis of hearing loss positively impacts children’s quality of life including language and cognitive development. Even though hearing loss associates with extremely high genetic and allelic heterogeneity, several studies have proven that Next-Generation Sequencin...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1264899/full |
| _version_ | 1797676875748737024 |
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| author | T. Imizcoz C. Prieto-Matos R. Manrique-Huarte D. Calavia A. Huarte P. C. Pruneda G. R. Ordoñez E. Cañada-Higueras A. Patiño-García A. Patiño-García G. Alkorta-Aranburu M. Manrique Rodríguez |
| author_facet | T. Imizcoz C. Prieto-Matos R. Manrique-Huarte D. Calavia A. Huarte P. C. Pruneda G. R. Ordoñez E. Cañada-Higueras A. Patiño-García A. Patiño-García G. Alkorta-Aranburu M. Manrique Rodríguez |
| author_sort | T. Imizcoz |
| collection | DOAJ |
| description | Background: An early etiological diagnosis of hearing loss positively impacts children’s quality of life including language and cognitive development. Even though hearing loss associates with extremely high genetic and allelic heterogeneity, several studies have proven that Next-Generation Sequencing (NGS)-based gene panel testing significantly reduces the time between onset and diagnosis.Methods: In order to assess the clinical utility of our custom NGS GHELP panel, the prevalence of pathogenic single nucleotide variants, indels or copy number variants was assessed by sequencing 171 nuclear and 8 mitochondrial genes in 155 Spanish individuals with hearing loss.Results: A genetic diagnosis of hearing loss was achieved in 34% (52/155) of the individuals (5 out of 52 were syndromic). Among the diagnosed cases, 87% (45/52) and 12% (6/52) associated with autosomal recessive and dominant inheritance patterns respectively; remarkably, 2% (1/52) associated with mitochondrial inheritance pattern. Although the most frequently mutated genes in this cohort were consistent with those described in the literature (GJB2, OTOF or MYO7A), causative variants in less frequent genes such as TMC1, FGF3 or mitCOX1 were also identified. Moreover, 5% of the diagnosed cases (3/52) were associated with pathogenic copy number variants.Conclusion: The clinical utility of NGS panels that allows identification of different types of pathogenic variants–not only single nucleotide variants/indels in both nuclear and mitochondrial genes but also copy number variants–has been demonstrated to reduce the clinical diagnostic odyssey in hearing loss. Thus, clinical implementation of genomic strategies within the regular clinical practice, and, more significantly, within the newborn screening protocols, is warranted. |
| first_indexed | 2024-03-11T22:36:46Z |
| format | Article |
| id | doaj.art-4b2cf02d573148bfb7fa2595e508ab61 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-11T22:36:46Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-4b2cf02d573148bfb7fa2595e508ab612023-09-22T13:26:34ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-09-011410.3389/fgene.2023.12648991264899Next-generation sequencing improves precision medicine in hearing lossT. Imizcoz0C. Prieto-Matos1R. Manrique-Huarte2D. Calavia3A. Huarte4P. C. Pruneda5G. R. Ordoñez6E. Cañada-Higueras7A. Patiño-García8A. Patiño-García9G. Alkorta-Aranburu10M. Manrique Rodríguez11CIMA LAB Diagnostics, University of Navarra, Pamplona, SpainDepartment of Otorhinolaryngology, University Clinic of Navarra, Pamplona, SpainDepartment of Otorhinolaryngology, University Clinic of Navarra, Pamplona, SpainDepartment of Otorhinolaryngology, University Clinic of Navarra, Pamplona, SpainDepartment of Otorhinolaryngology, University Clinic of Navarra, Pamplona, SpainDreamgenics S.L., Oviedo, SpainCentro de Secuenciación NASERTIC, Pamplona, SpainGenologica, Málaga, SpainCIMA LAB Diagnostics, University of Navarra, Pamplona, SpainDepartment of Pediatrics and Medical Genomics Unit, University Clinic of Navarra, Pamplona, SpainCIMA LAB Diagnostics, University of Navarra, Pamplona, SpainDepartment of Otorhinolaryngology, University Clinic of Navarra, Pamplona, SpainBackground: An early etiological diagnosis of hearing loss positively impacts children’s quality of life including language and cognitive development. Even though hearing loss associates with extremely high genetic and allelic heterogeneity, several studies have proven that Next-Generation Sequencing (NGS)-based gene panel testing significantly reduces the time between onset and diagnosis.Methods: In order to assess the clinical utility of our custom NGS GHELP panel, the prevalence of pathogenic single nucleotide variants, indels or copy number variants was assessed by sequencing 171 nuclear and 8 mitochondrial genes in 155 Spanish individuals with hearing loss.Results: A genetic diagnosis of hearing loss was achieved in 34% (52/155) of the individuals (5 out of 52 were syndromic). Among the diagnosed cases, 87% (45/52) and 12% (6/52) associated with autosomal recessive and dominant inheritance patterns respectively; remarkably, 2% (1/52) associated with mitochondrial inheritance pattern. Although the most frequently mutated genes in this cohort were consistent with those described in the literature (GJB2, OTOF or MYO7A), causative variants in less frequent genes such as TMC1, FGF3 or mitCOX1 were also identified. Moreover, 5% of the diagnosed cases (3/52) were associated with pathogenic copy number variants.Conclusion: The clinical utility of NGS panels that allows identification of different types of pathogenic variants–not only single nucleotide variants/indels in both nuclear and mitochondrial genes but also copy number variants–has been demonstrated to reduce the clinical diagnostic odyssey in hearing loss. Thus, clinical implementation of genomic strategies within the regular clinical practice, and, more significantly, within the newborn screening protocols, is warranted.https://www.frontiersin.org/articles/10.3389/fgene.2023.1264899/fullhearing lossdiagnosisNGSgene panelprecision medicine |
| spellingShingle | T. Imizcoz C. Prieto-Matos R. Manrique-Huarte D. Calavia A. Huarte P. C. Pruneda G. R. Ordoñez E. Cañada-Higueras A. Patiño-García A. Patiño-García G. Alkorta-Aranburu M. Manrique Rodríguez Next-generation sequencing improves precision medicine in hearing loss Frontiers in Genetics hearing loss diagnosis NGS gene panel precision medicine |
| title | Next-generation sequencing improves precision medicine in hearing loss |
| title_full | Next-generation sequencing improves precision medicine in hearing loss |
| title_fullStr | Next-generation sequencing improves precision medicine in hearing loss |
| title_full_unstemmed | Next-generation sequencing improves precision medicine in hearing loss |
| title_short | Next-generation sequencing improves precision medicine in hearing loss |
| title_sort | next generation sequencing improves precision medicine in hearing loss |
| topic | hearing loss diagnosis NGS gene panel precision medicine |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1264899/full |
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