• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2947-2951
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• 2015

Background: The phenomenon of occult carcinoma maybe observed in patients with clinically unilateral papillary thyroid microcarcinoma (PTMC). Although many studies have reported that the $BRAF^{T1799A}$ mutation is associated with aggressive PTMC, the relationship between $BRAF^{T1799A}$ mutation and occult carcinoma is unclear. The aim of this study was to investigate the risk factors, including $BRAF^{T1799A}$ mutation, for occult contralateral carcinoma in clinically unilateral PTMC accompanied by benign nodules in the contralateral lobe. Materials and Methods: From January 2011 to December 2013, we prospectively enrolled 89 consecutive PTMC patients with clinically unilateral carcinoma accompanied by benign nodules in the contralateral lobe who received a total thyroidectomy and cervical lymph node dissection. $BRAF^{T1799A}$ mutation was tested by pyrosequencing on postoperative paraffin specimens. The frequency and predictive factors for occult contralateral carcinoma were analyzed with respect to the following variables: age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or $BRAF^{T1799A}$ mutation. Results: A total of 36 patients (40.4%) had occult PTMC in the contralateral lobe. The median diameter of the occult tumors was $0.33{\pm}0.21cm$. The $BRAF^{T1799A}$ mutation was found in 38 cases (42.7%). According to the univariate analysis, there were no significant differences between the presence of occult contralateral carcinoma and age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or $BRAF^{T1799A}$ mutation. Conclusions: Using current methods, it is difficult to preoperatively identify patients with PTMC, and further research is needed to determine predictive factors for the presence of occult contralateral carcinoma in patients with unilateral PTMC.

• Clinical and Experimental Pediatrics
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• v.48 no.8
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• pp.877-880
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• 2005

Purpose : Glycogen storage disease type Ia(GSD Ia) is an autosomal recessive disorder caused by the deficiency of glucose-6-phosphatase(G6Pase). The aim of the study was to investigate the spectrum of G6Pase gene mutations and relationship between genotype and clinical findings in Korean patients with GSD Ia. Methods : Genomic DNA was extracted from peripheral leukocytes of 20 patients with GSD Ia. The five exons of G6Pase gene were amplified and PCR products were directly sequenced. The frequency of short stature, hypoglycemia, hypercholesterolemia, hyperuricemia, hypercalciuria, nephrocalcinosis and hepatic adenoma was compared between 727G>T homozygotes and 727G>T compound heterozygotes. Results : A total of 5 different mutations were identified. The most common mutation was the 727G>T with an allele frequency of 80%. All patients were either homozygous(12/20) or heterozygous(8/20) for the 727G>T mutation. G122D was found in 3 patients, P178A in 1, G222R in 2, and S339R in 2. There was no difference in the frequency of short stature, hypoglycemia, hypercholesterolemia, hyperuricemia, nephrocalcinosis, and hepatic adenoma between 727G>T homozygotes and heterozygotes. Conclusion : Diagnosis of GSD Ia can be based on clinical and biochemical abnormalities combined with mutation analysis instead of enzymatic diagnosis that requires liver biopsy. Homozygosity for the 727G>T does not seem to alter the disease phenotype as compared with the heterozygous state.

• Journal of Gastric Cancer
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• v.5 no.4 s.20
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• pp.260-265
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• 2005

Purpose: The protein kinase Chk1 is required for cell cycle arrest in response to DNA damage and is shown to play an important role in the G2/M checkpoint. The aim of this study was to investigate the relationship between microsatellite instability and frameshift mutation of the Chk1 gene in gastric cancers. Materials and Methods: The microsatellite instability was analyzed in 95 primary gastric carcinomas by using microdissection and 6 microsatellite markers. We also peformed single strand conformational polymorphism and sequencing to detect frameshift mutation of the Chk1 gene. Results: We found positive microsatellite instability in 19 (20%) of the 95 gastric cancers, 13 high- and 6 low-frequency microsatellite instability cases. The frameshift mutation of Chk1, which resulted in a truncated Chk1 protein, was detected in two high-frequency microsatellite instability cases. Conclusion: These data suggest that the microsatellite instability may contribute to the development of gastric carcinomas through inactivation of Chk1.

• Journal of Environmental Impact Assessment
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• v.22 no.2
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• pp.125-134
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• 2013

Plant virus coat (CP) gene-mediated protection is one of the best known approaches to protect against virus resistant transgenic plants. Transgenic N. benthamiana plants containing the CP gene of Zucchini green mottle mosaic virus (ZGMMV) were used for the environmental risk assessment of the living modified (LM) plants with plant virus resistance. The most optimal co-infection method of both ZGMMV and CMV (Cucumber mosaic virus) on Non-LM and CP-expressing LM tobacco plants was established and co-infection of CMV and ZGMMV was confirmed by polymerase chain reaction (PCR). To address the effects of LM tobacco plants on the mutation of the virus, in-vitro transcripts of CP and Replicase (Rep) derived from CMV and/or ZGMMV were inoculated onto Non-LM or LM tobacco plants. Mutation frequency of CP and Rep from CMV and ZGMMV was examined through six serial passages in Non-LM and LM tobacco plants. Little actual frequency of mutation was estimated, probably due to the limited number of transgenic plants tested in this study. However, it does not suggest environmental safety of these CP-mediated LM plants. Further study at a larger scale is needed to evaluate the environmental risk associated with the CP-expressing LM plants.

• Journal of Audiology & Otology
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• v.23 no.4
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• pp.175-180
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• 2019

Diagnosis of pre-lingual hearing loss (HL) is difficult owing to the high number of genes responsible. The most frequent cause of HL is DFNB1 due to mutations in the GJB2 gene. It represents up to 40% of HL cases in some populations. In Iran, it has previously been shown that DFNB1 accounts for 16-18% of cases but varies among different ethnic groups. Here, we reviewed results from our three previous publications and data from other published mutation reports to provide a comprehensive collection of data for GJB2 mutations and HL in northern Iran. In total, 903 unrelated families from six different provinces, viz., Gilan, Mazandaran, Golestan, Ghazvin, Semnan, and Tehran, were included and analyzed for the type and prevalence of GJB2 mutations. A total of 23 different genetic variants were detected from which 18 GJB2 mutations were identified. GJB2 mutations were 20.7% in the studied northern provinces, which was significantly higher than that reported in southern populations of Iran. Moreover, a gradient in the frequency of GJB2 mutations from north to south Iran was observed. c.35delG was the most common mutation, accounting for 58.4% of the cases studied. This study suggests that c.35delG mutation in GJB2 is the most important cause of HL in northern Iran.

• Korean Journal of Audiology
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• v.23 no.4
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• pp.175-180
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• 2019

Diagnosis of pre-lingual hearing loss (HL) is difficult owing to the high number of genes responsible. The most frequent cause of HL is DFNB1 due to mutations in the GJB2 gene. It represents up to 40% of HL cases in some populations. In Iran, it has previously been shown that DFNB1 accounts for 16-18% of cases but varies among different ethnic groups. Here, we reviewed results from our three previous publications and data from other published mutation reports to provide a comprehensive collection of data for GJB2 mutations and HL in northern Iran. In total, 903 unrelated families from six different provinces, viz., Gilan, Mazandaran, Golestan, Ghazvin, Semnan, and Tehran, were included and analyzed for the type and prevalence of GJB2 mutations. A total of 23 different genetic variants were detected from which 18 GJB2 mutations were identified. GJB2 mutations were 20.7% in the studied northern provinces, which was significantly higher than that reported in southern populations of Iran. Moreover, a gradient in the frequency of GJB2 mutations from north to south Iran was observed. c.35delG was the most common mutation, accounting for 58.4% of the cases studied. This study suggests that c.35delG mutation in GJB2 is the most important cause of HL in northern Iran.

• Molecular & Cellular Toxicology
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• v.2 no.4
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• pp.244-250
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• 2006

The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this respect, to regulate and to evaluate the chemical hazard will be important to environment and human health. The genotoxicity of 3 synthetic chemicals was evaluated in L5178Y $tk^{+/-}$ mouse lymphoma cells in vitro. 9H-carbazole (CAS No. 86-74-8) did not induce significant mutation frequencies both in the presence and absence of metabolic activation system. 1, 3-Dichloro-2-propanol (CAS No. 96-23-1) revealed a significant increase of mutation frequencies in the range of $625-373\;{\mu}g/mL$ in the absence of metabolic activation system and $157-79\;{\mu}g/mL$ in the presence of metabolic activation system. And also, fenpropathrin (CAS No. 64257-84-7) appeared the positive results only in the absence of metabolic activation system. Through the results of MLA tk assay with 3 synthetic chemicals in L5178Y cells in vitro, we may provide the important clues on the genotoxic potentials of these 3 chemicals.

• Journal of Genetic Medicine
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• v.10 no.1
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• pp.1-6
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• 2013

Chronic granulomatous disease (CGD) is a rare inherited disorder of a defective NADPH oxidase enzyme, resulting in very low or no production of superoxide and subsequent reactive oxygen species. Consequently, patients with CGD are highly susceptible to severe bacterial and fungal infections. CGD is a genetically heterogeneous disease caused by defects in any one of the genes encoding the NADPH oxidase components. CGD generally affects about 3-4 per 1,000,000 individuals; thus, it is surprising that the prevalence of CGD on Jeju Island is 34.3 per 1,000,000 individuals. At present, 20 patients with CGD from 14 unrelated families on Jeju Island have been identified; nine males and 11 females. All patients with CGD tested on Jeju Island had an identical and homozygous mutation (c.7C>T in CYBA, p.Q3X in $p22^{phox}$). Therefore, all patients were autosomal recessive form of CGD. This strongly suggests that the unique and identical mutation in CYBA may be inherited from a common proband. Using mutation-specific primers to detect the mutated allele in CYBA, the frequency of subjects carrying a mutated allele was 1.3% of enrolled subjects from Seogwipo City. Further studies are necessary to elucidate how frequently this mutant allele occurs in the population on Jeju Island. Additionally, it is important to construct a national registry system to understand the pathophysiology of CGD and develop a strategy for long-term therapy.

• BMB Reports
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• v.37 no.2
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• pp.234-238
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• 2004

This study was designed to investigate, in the Turkish population, the association of methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism and left ventricular hypertrophy (LVH) in patients with type II diabetes mellitus. Our study included 249 patients with type II diabetes mellitus (102 men, 147 women) and 214 healthy volunteers as controls (91 men, 123 women). MTHFR C677T genotypes were determined by polymerase chain reaction, restriction fragment length polymorphism techniques. No differences were observed in the distribution of MTHFR genotypes or allele frequencies in the cases versus the controls. The frequency of the MTHFR-mutated allele (T) was 31.7% in the type II diabetes mellitus versus 31.1% of the controls. The homozygous mutation (T/T) in the MTHFR gene was identified in 12% of the type II diabetes mellitus versus 9.3% of the controls. Patients with the TT genotype showed a higher prevalence of LVH when compared to patients with the CC and CT genotypes (p = 0.01). The MTHFR gene C677T mutation may be a possible risk factor for the development of LVH in the type II diabetic patients.

• Parasites, Hosts and Diseases
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• v.60 no.2
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• pp.109-116
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• 2022

Drug resistance is an important problem hindering malaria elimination in tropical areas. Point mutations in Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes confer resistance to antifolate drug, sulfadoxine-pyrimethamine (SP) while P. falciparum chloroquine-resistant transporter (Pfcrt) genes caused resistance to chloroquine (CQ). Decline in Pfdhfr/Pfdhps and Pfcrt mutations after withdrawal of SP and CQ has been reported. The aim of present study was to investigate the prevalence of Pfdhfr, Pfdhps, and Pfcrt mutation from 2 endemic areas of Thailand. All of 200 blood samples collected from western area (Thai-Myanmar) and southern area (Thai-Malaysian) contained multiple mutations in Pfdhfr and Pfdhps genes. The most prevalent haplotypes for Pfdhfr and Pfdhps were quadruple and double mutations, respectively. The quadruple and triple mutations of Pfdhfr and Pfdhps were common in western samples, whereas low frequency of triple and double mutations was found in southern samples, respectively. The Pfcrt 76T mutation was present in all samples examined. Malaria isolated from 2 different endemic regions of Thailand had high mutation rates in the Pfdhfr, Pfdhps, and Pfcrt genes. These findings highlighted the fixation of mutant alleles causing resistance of SP and CQ in this area. It is necessary to monitor the re-emergence of SP and CQ sensitive parasites in this area.