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Frequency of Usher gene mutations in non-syndromic hearing loss: higher variability of the Usher phenotype

Journal of Human Genetics volume 65, pages 855–864 (2020)Cite this article

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Abstract

Non-syndromic hearing loss (NSHL) is characterized by a vast genetic heterogeneity; some syndromic forms as Usher syndrome (USH) have onset as isolated deafness and then evolve later in life. We developed an NGS targeted gene-panel containing 59 genes and a customized bioinformatic pipeline for the analysis of DNA samples from clinically highly selected subjects with sensorineural hearing loss, previously resulted negative for GJB2 mutations/GJB6 deletions. Among the 217 tested subjects, 24 (11.1%) were found to carry mutations in genes involved both in NSHL and USH. For 6 out of 24 patients a diagnosis of USH was performed. Eleven subjects out of 24 had hearing loss without vestibular or ocular dysfunction and, due to their young age, it was not possible to establish whether their phenotype could be NSHL or USH. Seven subjects were diagnosed with NSHL, due to their age and phenotype. A total of 41 likely pathogenic/pathogenic mutations were identified, among which 17 novel ones. We report a high frequency of mutations in genes involved both in NSHL and in USH in a cohort of individuals tested for seemingly isolated deafness. Our data also highlight a wider than expected phenotypic variability in the USH phenotype.

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Acknowledgements

The authors wish to thank the family members for their active participation in the study.

Author information

Authors and Affiliations

  1. Laboratory of Molecular Genetics of Neurodevelopment, Department of Women’s and Children’s Health, University of Padua, Padua, Italy

    Federica Cesca, Elisa Bettella, Roberta Polli, Emanuela Leonardi, Maria Cristina Aspromonte & Alessandra Murgia

  2. Fondazione Istituto di Ricerca Pediatrica (IRP), Città della Speranza, Padua, Italy

    Federica Cesca, Elisa Bettella, Roberta Polli, Emanuela Leonardi, Maria Cristina Aspromonte & Alessandra Murgia

  3. Medical Center of Phoniatrics, Casa di Cura Trieste, Padua, Italy

    Barbara Sicilian

  4. Genetic Counseling Service, Regional Hospital of Bolzano, Bolzano, Italy

    Franco Stanzial & Francesco Benedicenti

  5. U.O. Medical Genetics Romagna, AULS Romagna, Cesena, Italy

    Alberto Sensi

  6. ENT and Audiology Department, University Hospital of Ferrara, Ferrara, Italy

    Andrea Ciorba

  7. Medical Genetics Unit, University Hospital of Ferrara, Ferrara, Italy

    Stefania Bigoni

  8. Department of Neurosciences, University of Padua, Padua, Italy

    Elona Cama, Pietro Scimemi & Rosamaria Santarelli

  9. Audiology Service, Santi Giovanni e Paolo Hospital, ULSS3 Serenissima, Venice, Italy

    Elona Cama, Pietro Scimemi & Rosamaria Santarelli

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  1. Federica Cesca
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  2. Elisa Bettella
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  8. Francesco Benedicenti
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  10. Andrea Ciorba
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Correspondence to Alessandra Murgia.

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Cesca, F., Bettella, E., Polli, R. et al. Frequency of Usher gene mutations in non-syndromic hearing loss: higher variability of the Usher phenotype. J Hum Genet 65, 855–864 (2020). https://doi.org/10.1038/s10038-020-0783-1

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