Background and ObjectivesAutosomal recessive non-syndromic hearing loss (ARNSHL) with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations in gap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find the contribution of GJB2 gene mutations with the genotype-phenotype correlations in 45 ARNSHL cases in the Kurdish population.Subjects and MethodsGenomic DNA was extracted from a total of 45 ARNSHL families. The linkage analysis with 3 short tandem repeat markers linked to GJB2 was performed on 45 ARNSHL families. Only 9 of these families were linked to the DFNB1 locus. All the 45 families who took part were sequenced for confirmation linkage analysis (to perform a large project).ResultsA total of three different mutations were determined. Two of which [c.35delG and c.-23+1G>A (IVS1+1G>A)] were previously reported but (c.299-300delAT) mutation was novel in the Kurdish population. The homozygous pathogenic mutations of GJB2 gene was observed in nine out of the 45 families (20%), also heterozygous genotype (c.35delG/N)+(c.-23+1G>A/c.-23+1G>A) were observed in 4/45 families (8.8%). The degree of hearing loss (HL) in patients with other mutations was less severe than patients with c.35delG homozygous mutation (p<0.001).ConclusionsOur data suggest that GJB2 mutations constitute 20% of the etiology of ARNSHL in Iran; moreover, the c.35delG mutation is the most common HL cause in the Kurdish population. Therefore, these mutations should be included in the molecular testing of HL in this population.

This study aimed to investigate the effect of crocin consumption, high-intensity interval training (HIIT), and low-intensity continuous training (LICT) and their interactive effect on the gene expression of Mfn2 and Drp1 in the skeletal muscle and serum glucose and insulin indices in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic rats. Fifty-six adult rats were divided into eight groups of seven subjects: crocin consumption, HIIT, LICT, HIIT with crocin, LICT with crocin, diabetic control, healthy control, and sham (placebo). At the end of the course (5 months), metabolic indices were measured. Moreover, the Mfn2 and Drp1 gene expression levels in all groups were measured using RT-PCR. The statistical analysis showed that in the exercise training (HIIT and LICT) and the crocin consumption groups, the glucose and insulin indices significantly improved (p = .005). Moreover, in these groups, the levels of gene expression of Mfn2 and Drp1 significantly increased and decreased, respectively (p = .001). Exercise training and crocin consumption appear to, either in combination or individually, have a beneficial effect on mitochondrial dynamics and diabetes by improving the mitochondrial fusion and fission indices (Mfn2 and Drp1), and by modifying the insulin resistance index and glucose homeostasis. Practical applicationsMfn2 and Drp1, as the main regulators of the mitochondrial fusion and fission, play an important role in maintaining mitochondrial dynamics and type 2 diabetes. Thus, the regulation of mitochondrial dynamics is an intricate process that retains the balance between mitochondrial fission and fusion, and any disturbance in this balance can lead to mitochondrial-associated diseases including insulin resistance and T2D. There is evidence that herbal antioxidants Including crocin and exercise training help improve the mitochondrial activity and insulin sensitivity in T2D. Considering the importance of the two Drp1 and Mfn1 genes in the mitochondrial dynamic pathway and coding the proteins that play a key role in relation to T2D, this study primarily examined the interactive effects of endurance training (HIIT and LICT) along with crocin consumption on the expression the genes mentioned above; the results obtained in this study can provide a new approach to the treatment of HFD + STZ-induced diabetic rats. K E Y W O R D Scrocin, Drp1, Mfn2, T2D, training

Objective: Keratoconus (KC) is an eye disorder in which the cornea is swollen, thinned and deformed. Despite extensive studies, the pathophysiological processes and genetic etiology of KC are unknown. The disease incidence is approximately 1 in 2,000, and it is the most common cause of corneal transplantation in the USA. Many genes are involved in the disease, but evidence suggests a major role for VSX1 in the etiology of KC. This study aimed to determine the frequency of mutations in exons 2, 3 and 4 of the VSX1 gene in Chaharmahal va Bakhtiari province in the southwest of Iran. Study Design: In this experimental study, mutations in 3 exons, namely exons 2, 3 and 4, of VSX1 were investigated in 50 patients with KC and 50 healthy control subjects. DNA was extracted using a standard phenol-chloroform method. PCR-single-strand conformational polymorphism/heteroduplex analysis was performed, followed by DNA sequencing to confirm the identified motility shifts. Results: H244R mutations were found in 1 patient and also in 1 healthy control subject. Furthermore, 12 polymorphisms were identified in patients with KC and 7 in healthy control subjects [rs6138482 and c.546A>G (rs12480307)]. Conclusion: Our investigation showed that KC-related VSX1 mutations were found in a very small proportion of the studied patients from Iran. Further investigations on other genes are needed to clarify their roles in KC pathogenesis.