Novel homozygous variant in the PDZD7 gene in a family with nonsyndromic sensorineural hearing loss

Abstract

Hearing loss is the most common sensory neural disorder in humans, and according to a WHO estimation, 5.5% (466 million) of people worldwide have disabling hearing loss. In this study, a Chinese family with prelingual sensorineural hearing loss was investigated. The affected individuals showed moderately severe hearing loss at all frequencies. Using target genome enrichment and high-throughput sequencing, the homozygous variant c.2372del; p.(Ser791fs) was identified in PDZD7. This variant lies in exon 15 of PDZD7 and results in a frame shift followed by an early stop codon. It is classified as pathogenic according to the ACMG/AMP guidelines and ClinGen specifications. Our study expands the pathogenic variant spectrum of PDZD7 and strengthens the clinical importance of this gene in patients with moderately severe hearing loss.

Clinical characterizations and molecular genetic study of two co-segregating variants in PDZD7 and PDE6C genes leading simultaneously to non-syndromic hearing loss and achromatopsia

“…This gene encodes a protein containing four domains, three PDZ and one HHD (harmonin homology domain). While the PDZ3 only interacts with WHRN, the other two PDZ domains have important role in interacting with other Usher quaternary protein complex components USH2A, ADGRV1 and WHRN [ 24 ]. This interaction and the proper function of these proteins are essential for development and correct performance of both auditory and visual systems [ 25 ].…”