Artikel ; Online: Highly variable hearing loss due to POU4F3 (c.37del) is revealed by longitudinal, frequency specific analyses.
European journal of human genetics : EJHG
2023 Band 31, Heft 7, Seite(n) 815–823
Abstract: Genotype-phenotype correlations add value to the management of families with hereditary hearing loss (HL), where age-related typical audiograms (ARTAs) are generated from cross-sectional regression equations and used to predict the audiogram phenotype ... ...
Abstract | Genotype-phenotype correlations add value to the management of families with hereditary hearing loss (HL), where age-related typical audiograms (ARTAs) are generated from cross-sectional regression equations and used to predict the audiogram phenotype across the lifespan. A seven-generation kindred with autosomal dominant sensorineural HL (ADSNHL) was recruited and a novel pathogenic variant in POU4F3 (c.37del) was identified by combining linkage analysis with whole exome sequencing (WES). POU4F3 is noted for large intrafamilial variation including the age of onset of HL, audiogram configuration and presence of vestibular impairment. Sequential audiograms and longitudinal analyses reveal highly variable audiogram features among POU4F3 (c.37del) carriers, limiting the utility of ARTAs for clinical prognosis and management of HL. Furthermore, a comparison of ARTAs against three previously published families (1 Israeli Jewish, 2 Dutch) reveals significant interfamilial differences, with earlier onset and slower deterioration. This is the first published report of a North American family with ADSNHL due to POU4F3, the first report of the pathogenic c.37del variant, and the first study to conduct longitudinal analysis, extending the phenotypic spectrum of DFNA15. |
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Mesh-Begriff(e) | Humans ; Cross-Sectional Studies ; Homeodomain Proteins/genetics ; Hearing Loss/genetics ; Hearing Loss, Sensorineural/diagnosis ; Hearing Loss, Sensorineural/genetics ; Hearing Loss, Sensorineural/pathology ; Deafness ; Pedigree ; Transcription Factor Brn-3C/genetics |
Chemische Substanzen | Homeodomain Proteins ; POU4F3 protein, human ; Transcription Factor Brn-3C |
Sprache | Englisch |
Erscheinungsdatum | 2023-04-19 |
Erscheinungsland | England |
Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 1141470-4 |
ISSN | 1476-5438 ; 1018-4813 |
ISSN (online) | 1476-5438 |
ISSN | 1018-4813 |
DOI | 10.1038/s41431-023-01358-0 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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