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A novel nonsense variant in the CENPP gene segregates in a Swiss family with autosomal dominant low-frequency sensorineural hearing loss


Low-frequency sensorineural hearing loss (SNHL) is a rare hearing impairment affecting frequencies below 1000 Hz, previously associated with DIAPH1, WSF1, MYO7A, TNC, SLC26A4 or CCDC50 genes. By exome sequencing, we report a novel nonsense variant in CENPP gene, segregating low-frequency SNHL in five affected members in a Swiss family with autosomal dominant inheritance pattern. Audiological evaluation showed up-sloping audiometric configuration with mild-to-moderate losses below 1000 Hz, that progresses to high-frequencies over time. Protein modeling shows that the variant truncates five amino acids at the end, losing electrostatic interactions that alter protein stability. CENPP gene is expressed in the supporting cells of the organ of Corti and takes part as a subunit of the Constitutive Centromere Associated Network in the kinetochore, that fixes the centromere to the spindle microtubules. We report CENPP as a new candidate gene for low-frequency SNHL. Further functional characterization might enable us to elucidate its molecular role in SNHL.

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Fig. 1: CENPP associated with low frequency sensorineural hearing loss (SNHL).

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information file. Anonymized familial variant dataset is available from the corresponding author on reasonable request. The CENPP structural model was submitted to the ModelArchive database (; Public access after publication. Temporary access code: FUxtQ7paHI).


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We would like to thank the patients of this family for their enthusiastic participation.


This project was partially funded by H2020-SC1-2019-848261: Unification of Treatments and Interventions for Tinnitus Patients—UNITI; and the Swiss Schmieder-Bohrisch Foundation. JAL-E is partially funded by the Asociacion Sindrome de Meniere España (ASMES) and Meniere Society, UK. PR-B is a PhD student in the Biomedicine Program at Universidad de Granada and his salary was supported by H2020-SC1-2019-848261. DB is supported by a national MD-PhD scholarship from the Swiss National Science Foundation. Additional funding:- Papel de la regulación epigenómica en la penetrancia y expresividad en la enfermedad de Meniere (EPIMEN) - CECEU PY20-00303.- Regional Ministry of Economic Transformation, Industry, Knowledge, and Universities of Junta de Andalucía - PREDOC2021/00343.- Career development grant (“Filling the Gap”) from the University of Zurich, Switzerland.

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AE and DB recruited and obtained clinical data from the family. PR-B, PR-N, and AE-B conducted DNA extraction and quality controls. PR-B, AE-B and AG-M performed bioinformatics analyses in WES data. AMP-P performed the protein modeling. PR-B and JAL-E drafted the manuscript. All authors approved the final version of the manuscript.

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Correspondence to Jose A. Lopez-Escamez.

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The authors declare no competing interests.

Ethical approval

This study involves human participants and was approved by the local Ethical Committee (KEK-ZH-Nr. 2019-01006, Kantonale Ethikkommission, Zurich, Switzerland) in accordance with the Helsinki declaration and its amendments. Written informed general consent was obtained from all participants.

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Robles-Bolivar, P., Bächinger, D., Parra-Perez, A.M. et al. A novel nonsense variant in the CENPP gene segregates in a Swiss family with autosomal dominant low-frequency sensorineural hearing loss. Eur J Hum Genet 30, 1301–1305 (2022).

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