Phenotypic variability in a seven-generation Swedish family segregating autosomal dominant hearing impairment due to a novel EYA4 frameshift mutation
| Autor: | Hanna Arnesson, Lisbeth Tranebjærg, Anna-Carin Rehnman, Niklas Dahl, Ulla Wedén, Nanna Dahl Rendtorff, Joakim Klar, Marianne Lodahl, Carina Frykholm |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Genetic Linkage Hearing loss Hearing Loss Sensorineural Locus (genetics) Biology Frameshift mutation Young Adult Genetic linkage Genetics medicine Humans Child Frameshift Mutation Hearing Loss Genes Dominant Sweden Dilated cardiomyopathy General Medicine medicine.disease Pedigree Phenotype Child Preschool Trans-Activators Medical genetics Female Age of onset medicine.symptom Cardiomyopathies Haploinsufficiency |
| Zdroj: | Gene. 563:10-16 |
| ISSN: | 0378-1119 |
| Popis: | Linkage to an interval overlapping the DFNA10 locus on chromosome 6q22-23 was found through genome wide linkage analysis in a seven-generation Swedish family segregating postlingual, autosomal dominant nonsyndromic sensorineural hearing impairment. A novel heterozygous frame-shift mutation (c.579_580insTACC, p.(Asp194Tyrfs*52)) in EYA4 was identified that truncates the so-called variable region of the protein. The mutation is predicted to result in haploinsufficiency of the EYA4 product. No evidence for dilated cardiomyopathy was found in the family, contrasting to a previous family with a deletion resulting in a similar truncation in the variable region. A highly variable age of onset was seen in the mutation carriers. For assessment of the aetiology of this variability, clinical and audiometric data analyses were performed. The affected family members all had similar cross-sectional and longitudinal deterioration of pure tone average (PTA) once the process of hearing deterioration had started, and no gender, parent-of-origin or family branch differences on PTA could be found. Age at onset varied between the family branches. In summary, this is the ninth published genetically verified DFNA10 family. The results imply that unidentified factors, genetic or environmental, other than the EYA4 mutation, are of importance for the age at onset of DFNA10, and that mutation early in the variable region of the EYA4 protein can occur in the absence of dilated cardiomyopathy. |
| Databáze: | OpenAIRE |
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