Analysis of Rotterdam Study cohorts confirms a previously identified RIPOR2 in-frame deletion as a prevalent genetic factor in phenotypically variable adult-onset hearing loss (DFNA21) in the Netherlands
© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ..
BACKGROUND: A 12-nucleotide RIPOR2 in-frame deletion was recently identified as a relatively common and highly penetrant cause of autosomal dominant non-syndromic sensorineural hearing loss, type DFNA21, in the Netherlands. The associated hearing phenotype is variable. The allele frequency (AF) of 0.039% of this variant was determined in a local cohort, and the reported phenotype may be biased because studied families were identified based on index patients with hearing loss (HL). In this study, we determine the AF in a cohort from a different geographical region of the Netherlands. Additionally, we examine the hearing phenotype in individuals with the variant but not selected for HL.
METHODS: The AF was determined in participants of the Rotterdam Study (RS), a large cohort study. The phenotype was characterised using individual clinical hearing data, including audiograms.
RESULTS: The observed AF in the RS cohort was 0.072% and not statistically significantly different from the previously observed 0.039%. The AF in the two cohorts combined was 0.052%. Consistent with previous findings, we found a highly variable audiometric phenotype with non-penetrance of HL in 40% of subjects aged 55-81, which is higher than the 10% at age 50 previously observed.
CONCLUSION: We found an overall higher AF and lower penetrance than previously reported, confirming that DFNA21 is relatively common in the Netherlands. This supports its potential suitability as a target for therapeutic development. Studying possible modifying factors is essential to explain the phenotypical variability and to identify patients eligible for such a therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:60 |
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| Enthalten in: |
Journal of medical genetics - 60(2023), 11 vom: 20. Nov., Seite 1061-1066 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Velde, Hedwig M [VerfasserIn] |
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| Links: |
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| Themen: |
Genetics, Medical |
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| Anmerkungen: |
Date Revised 24.10.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1136/jmg-2023-109146 |
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| Förderinstitution / Projekttitel: |
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NLM356675386 |
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| 245 | 1 | 0 | |a Analysis of Rotterdam Study cohorts confirms a previously identified RIPOR2 in-frame deletion as a prevalent genetic factor in phenotypically variable adult-onset hearing loss (DFNA21) in the Netherlands |
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| 500 | |a Citation Status Publisher | ||
| 520 | |a © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a BACKGROUND: A 12-nucleotide RIPOR2 in-frame deletion was recently identified as a relatively common and highly penetrant cause of autosomal dominant non-syndromic sensorineural hearing loss, type DFNA21, in the Netherlands. The associated hearing phenotype is variable. The allele frequency (AF) of 0.039% of this variant was determined in a local cohort, and the reported phenotype may be biased because studied families were identified based on index patients with hearing loss (HL). In this study, we determine the AF in a cohort from a different geographical region of the Netherlands. Additionally, we examine the hearing phenotype in individuals with the variant but not selected for HL | ||
| 520 | |a METHODS: The AF was determined in participants of the Rotterdam Study (RS), a large cohort study. The phenotype was characterised using individual clinical hearing data, including audiograms | ||
| 520 | |a RESULTS: The observed AF in the RS cohort was 0.072% and not statistically significantly different from the previously observed 0.039%. The AF in the two cohorts combined was 0.052%. Consistent with previous findings, we found a highly variable audiometric phenotype with non-penetrance of HL in 40% of subjects aged 55-81, which is higher than the 10% at age 50 previously observed | ||
| 520 | |a CONCLUSION: We found an overall higher AF and lower penetrance than previously reported, confirming that DFNA21 is relatively common in the Netherlands. This supports its potential suitability as a target for therapeutic development. Studying possible modifying factors is essential to explain the phenotypical variability and to identify patients eligible for such a therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Genetics, Medical | |
| 650 | 4 | |a Heredity | |
| 650 | 4 | |a Human Genetics | |
| 650 | 4 | |a Otolaryngology | |
| 650 | 4 | |a Otorhinolaryngologic Diseases | |
| 700 | 1 | |a Homans, Nienke C |e verfasserin |4 aut | |
| 700 | 1 | |a Goedegebure, André |e verfasserin |4 aut | |
| 700 | 1 | |a Lanting, Cornelis P |e verfasserin |4 aut | |
| 700 | 1 | |a Pennings, Ronald J E |e verfasserin |4 aut | |
| 700 | 1 | |a Kremer, Hannie |e verfasserin |4 aut | |
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