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

ABSTRACT: 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.

SUBMITTER: Robles-Bolivar P 

PROVIDER: S-EPMC9626507 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature