Finding and computational analyses of a novel mutation in CEP78 linked to cone-rod dystrophy and hearing loss

Cone-Rod Dystrophy with Hearing Loss (CRDHL) is a rare genetic disorder marked by progressive vision and hearing loss. This research explores the genetic changes observed in patients with CRDHL and their subsequent influence on protein functionality. Whole-exome sequencing (WES) was utilized to investigate CRDHL. Carrier screening was performed using Tetra-primer ARMS PCR on 98 relatives, with subsequent Sanger sequencing to confirm the results. Bioinformatics analyses were conducted to explore the mutation's potential impact on protein structure and function. This study finds a novel CEP78 mutation, c.328A > T, p.Lys110* through WES. The c.328A > T mutation truncated the CEP78 protein from 689 to 110 amino acids. Among 98 relatives screened, 17 were identified as carriers. Affected individuals exhibited progressive vision and hearing loss. Bioinformatics analyses showed significant structural changes in the mutant protein, including loss of functional domains and conserved regions. Molecular modeling revealed reduced stability and increased flexibility, impairing protein functionality and highlighting its role in disease progression. This study highlights the c.328A > T mutation in CEP78 as a critical contributor to CRDHL. The findings emphasize the importance of genetic testing in early diagnosis and carrier identification. At the same time, bioinformatics analyses provide a foundation for potential therapeutic strategies to mitigate this mutation's impact.