Investigation of MYO15A and MYO7A Mutations in Iranian Patients with Nonsyndromic Hearing Loss.

BACKGROUND: Hearing loss (HL) is the most common sensory disorder in humans, which affects individuals in both inherited and acquired forms. MYO15A and MYO7A gene mutations have a significant role in the development of deafness. In this study, we assessed the prevalence of MYO15A and MYO7A mutations in one hundred non-relative deaf Iranians. Materials and methods: The existence of MYO15A and MYO7A mutations were assessed using the tetra-primer ARMS-PCR method, High Resolution Melting (HRM) and sequencing method. Results: A heterozygote missense mutation, p.V2135L (c.6403G > T) in the MYO15A gene, was found in a patient using the sequencing method. Conclusion: These results explain the negligible prevalence of selected mutations among Iranian patients. Identifying common mutations in patients of an ethnic group can reduce the financial costs and time needed for identifying the causes of deafness.

The worldwide frequency of MYO15A gene mutations in patients with non-syndromic hearing loss: A meta-analysis.

MYO15A is the third most crucial gene in hereditary sensorineural hearing loss after GJB2 and SLC26A4. In the present study, we reviewed the prevalence of MYO15A mutations in patients with autosomal recessive non-syndromic hearing loss (ARNSHL). In this meta-analysis, we conducted a search of PubMed, Web of Science, Excerpta Medica Database, and Scopus, and identified the articles up to September 2019 without any time limit. Two investigators independently selected the relevant papers and extracted the required information. A total of 44 case-control and case series studies were considered, and 4176 patients and 3706 healthy individuals, as the control group, were included. The pooled frequency of MYO15A mutations between patients suffering from ARNSHL was calculated as 6.2% (95% CI: 4.9-7.8, P-value<0.001). There was heterogeneity between our studies (P-value<0.001, I2=58.1%); therefore, the random-effects model was utilized for analysis. Given the results, in many countries, the MYO15A gene has a significant contribution to hearing loss. Moreover, in several regions, specific dominant mutations in this gene have been reported. Therefore, the ethnic background should be considered to investigate the mutations of the MYO15A gene.

PD-1/PD-L1 pathway: Basic biology and role in cancer immunotherapy.

Over the course of past few years, cancer immunotherapy has been accompanied with promising results. However, preliminary investigations with respect to immunotherapy concentrated mostly on targeting the immune checkpoints, nowadays, emerge as the most efficient strategy to raise beneficial antitumor immune responses. Programmed cell death protein 1 (PD-1) plays an important role in subsiding immune responses and promoting self-tolerance through suppressing the activity of T cells and promoting differentiation of regulatory T cells. PD-1 is considered as an immune checkpoint and protects against autoimmune responses through both induction of apoptosis in antigen-specific T cells and inhibiting apoptosis in regulatory T cells. Several clinical trials exerting PD-1 monoclonal antibodies as well as other immune-checkpoint blockades have had prosperous outcomes and opened new horizons in tumor immunotherapy. Nonetheless, a bulk of patients have failed to respond to these newly emerging immune-based approach and the survival rate was not satisfying. Additional strategies, especially combination therapies, has been initiated and been further promising. Attempts to identify novel and well-suited predictive biomarkers are also sensed. In this review, the promotion of cancer immunotherapy targeting PD-1 immunoinhibitory pathway is discussed.