Mutations in GJB2 as Major Causes of Autosomal Recessive Non-Syndromic Hearing Loss: First Report of c.299-300delAT Mutation in Kurdish Population of Iran

BACKGROUND AND OBJECTIVES: Autosomal 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 METHODS: Genomic 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). RESULTS: A 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). CONCLUSIONS: Our 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.

[ effect of immobilization stress and cold stress on growth of WEHI: 164 fibrosarcoma cells in Balb/c mice]

Stress gradually suppresses the immune system making the body susceptible to various diseases. The aim of this study was to show the effects of cold and immobilization stress on growth of malignant cells in Balb/c mice. In an experimental study which was carried out in the Molecular and Cellular Research Center of Shahrekord University of Medical Sciences in 2008, 3 groups of 10 Balb/c mice were selected to investigate the effects of cold stress and immobilization stress on growth of WEHI - 164 fibrosarcoma cells in groups of 10, Balb/c mice. Each mouse was injected with tumor cells subcutaneously in the chest; for 2 hours/day mice in group 1 were subjected to cold stress and mice in group 2 were immobilized; the control group received tumor cells with no stresses. Tumor sizes were measured every two days and case groups were compared with the control group. Results showed that the tumor sizes in stressed mice were significantly different from controls. After 14 days of tumor inoculation, mean tumor size in mice subjected to cold stress and immobilization was 31.99 +/- 2.61 and 37.13 +/- 3.51cumm respectively, but in the control group the mean tumor size was 18.15 +/- 3.09 cumm, [p<0.05]. Results in this study showed that cold and immobilization stresses increase the growth of WEHI-164 tumor cells