• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.149-153
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• 2016

Breast cancer is the most common cancer in Iran. In the recent years an upward trend has been observed in the Iranian population. Early detection by molecular approaches may reduce breast cancer morbidity and mortality. We provided consultation to 3,782 women diagnosed with early onset breast cancer during the past 15 years (1999-2014). To establish a data set for BRCA gene alterations of the Iranian families at risk, two hundred and fifty four women who met our criteria were analyzed. A total number of 46 alterations including 18 variants with unknown clinical significance (39.1%), 18 missense mutations (39.1%), 7 Indels (15.2%) and 3 large rearrangement sequences (6%) were identified. Further scanning of affected families revealed that 49% of healthy relatives harbor identical causative mutations. This is the first report of comprehensive BRCA analysis in Iranian women with early onset breast cancer. Our findings provide valuable molecular data to support physicians as well as patients for the best decision making on disease management.

• Journal of The Korean Society of Inherited Metabolic disease
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• 제13권1호
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• pp.48-53
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• 2013

Tyrosinemia I (fumarylacetoacetate hydrolase deficiency) is an autosomal recessive inborn error of tyrosine metabolism that produces liver failure in infancy or a more chronic course of liver disease with cirrhosis, often complicated by hepatocellular carcinoma in childhood or early adolescence. We studied a 37-year-old woman with tyrosinemia I whose severe liver disease in infancy and rickets during childhood were resolved with dietary therapy. From 14 years of age, she resumed unrestricted diet with the continued presence of the biochemical features of tyrosinemia, yet maintained normal liver function. In adult years, she accumulated only a small amount of succinylacetone. Despite this evolution to a mild biochemical and clinical phenotype, she eventually developed hepatocellular carcinoma. Her fumarylacetoacetate hydrolase genotype consists of a splice mutation, IVS6-1G>T, and a novel missense mutation, p.Q279R. Studies of resected liver revealed the absence of hydrolytic activity and immunological expression of fumarylacetoacetate hydrolase in tumour. In the non-tumoral areas, however, 53% of normal hydrolytic activity and immunologically present fumarylacetoacetate hydrolase were found. This case demonstrates the high risk of liver cancer in tyrosinemia I even in a seemingly favorable biological environment. In this study of tyrosinemia I, Case 2 with negative succinylacetone accumulation and the recovery of acute liver failure was compared with Case 1. Diet restriction and NTBC treatment are crucial to prevent hepatocellular carcinoma until liver transplant can take place and cure the condition. Further studies are needed to examine cases where liver cancer did not result despite clinical symptoms/signs of tyrosinemia type I.

• Journal of Microbiology and Biotechnology
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• 제18권11호
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• pp.1853-1857
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• 2008

Salmonella contamination in chicken meat was studied with 100 chicken meat samples purchased from 55 shops located in various regions. A total of 21 isolates of Salmonella enterica were isolated from 21 chicken meat samples from four shops located at open markets, whereas there were none from supermarkets with well-equipped cold systems. Among these, 18 isolates were identified as Salmonella enterica serotype Haardt (S. Haardt) and three isolates were S. enterica serotype Muenchen. When the minimal inhibitory concentrations of the S. Haardt isolates were assayed with the agar dilution method to determine susceptibility to ampicillin, chloramphenicol, sulfisoxazole, tetracycline, and nalidixic acid, all 18 isolates were resistant to tetracycline and nalidixic acid and nine of these were resistant to ampicillin. These isolates showed reduced susceptibility to eight fluoroquinolones including ciprofloxacin, enrofloxacin, levofloxacin, gatifloxacin, gemifloxacin, moxifloxacin, norfloxacin, and ofloxacin. When quinolone resistance determining regions of gyrA and gyrB were sequenced, every isolate had the same missense mutation Ser83$\rightarrow$Tyr (TCC$\rightarrow$+TAC) in gyrA, whereas no mutation was found in gyrB. Pulsed-field gel electrophoresis with XbaI revealed a close relationship among these isolates, suggesting a contamination of raw chicken meat with clonal spread of nalidixic acid-resistant and quinolone-reduced susceptibility S. Haardt in chickens. Results in this study show the importance of a well-equipped cold system and the prudent use of fluoroquinolone in chickens to prevent the occurrence of quinolone-resistant isolates.

• Clinical and Experimental Reproductive Medicine
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• 제27권3호
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• pp.291-294
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• 2000

연구목적: 본 연구는 자궁내막증과 다낭성 난포증후군 불임환자들을 대상으로 $LH{\beta}$ exon 3 (Gly102Ser) 유전자의 돌연변이를 탐색하고자 시도하였다. 연구재료 및 방법: 그 대상으로 26명의 자궁내막증 환자와 52명의 다낭성 난포증후군 환자 그리고, 50명의 출산 경험이 있는 건강한 여성을 대조군으로 사용하였다. 이들을 대상으로 한 돌연변이 탐색은 PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) 방법으로 수행되었다. 결과 : 그 결과 자궁내막증과 다낭성 난포증후군 환자 및 출산 경험이 있는 건강한 여성에서 그 변이형이 나타나지 않았다. 결론: 따라서, 자궁내막증과 다낭성 난포증후군 불임환자의 $LH{\beta}$ exon 3 돌연변이형은 중국인 집단에만 존재할 가능성이 높으며, 더 많은 불임환자들을 대상으로 한 연구가 요구된다.

• Journal of Genetic Medicine
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• 제8권2호
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• pp.125-129
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• 2011

Stickler syndrome is a very rare connective tissue disorder. The authors of the present study describe an 11-month-old girl with high myopia, retinal abnormalities, flat nose, cleft palate, retrognathia, micrognathia, short stature and arthrogryposis. Radiological evaluation also showed irregularity of the epiphysis of the femur and tibia and spondyloepiphyseal dysplasia. Genetic analysis using a peripheral blood sample revealed a novel variant c.787G>A (p.Gly246Asp) mutation of the COL2A1 gene. This is the first Korean case with Stickler syndrome confirmed by genetic testing.

• Journal of Genetic Medicine
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• 제6권1호
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• pp.81-86
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• 2009

Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous chondroplasia, characterized by delayed development of the ossification centers and, deformities of the extremities that involve only the epiphysis and result in mild short stature. Mutations in the cartilage oligomeric matrix protein (COMP) gene are most commonly found, and most of the mutations are located in the calmodulin-like repeats and the C-terminal domain. We report a Korean kindred of 12 family members with MED in four generations who were found to have a novel mutation in the COMP gene. A pedigree showed early onset osteoarthritis requiring arthroplasty that was an autosomal dominant inherited trait. Radiological examinations demonstrated the presence of osteochondral defects in the medial femoral condyles, and the knee and hip joints showed variable degrees of precocious degenerative changes. Mutation analysis of the COMP gene in the proband and five other affected family members identified a novel missense mutation, c.1280G>C (p.Gly427Ala) in exon 12, which was not found in three unaffected family members. Direct sequencing of the COMP gene may yield pathogenic mutations in dominantly inherited MED cases, and may provide opportunities of carrier detection among high-risk family members, leading to genetic counseling for early diagnosis and intervention before the onset of complications.

• Molecules and Cells
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• 제20권3호
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• pp.385-391
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• 2005

As a first step towards identifying genes involving in the signal transduction pathways mediating rice blast resistance, we isolated 3 mutants lines that showed enhanced susceptibility to rice blast KJ105 (91-033) from a T-DNA insertion library of the japonica rice cultivar, Hwayeong. Since none of the susceptible phenotypes co-segregated with the T-DNA insertion we adapted a map-based cloning strategy to isolate the gene(s) responsible for the enhanced susceptibility of the Hwayeong mutants. A genetic mapping population was produced by crossing the resistant wild type Hwayeong with the susceptible cultivar, Nagdong. Chi-square analysis of the $F_2$ segregating population indicated that resistance in Hwayeong was controlled by a single major gene that we tentatively named Pi-hy. Randomly selected susceptible plants in the $F_2$ population were used to build an initial map of Pi-hy. The SSLP marker RM2265 on chromosome 2 was closely linked to resistance. High resolution mapping using 105 $F_2$ plants revealed that the resistance gene was tightly linked, or identical, to Pib, a resistance gene with a nucleotide binding sequence and leucine-rich repeats (NB-LRR) previously isolated. Sequence analysis of the Pib locus amplified from three susceptible mutants revealed lesions within this gene, demonstrating that the Pi-hy gene is Pib. The Pib mutations in 1D-22-10-13, 1D-54-16-8, and 1C-143-16-1 were, respectively, a missense mutation in the conserved NB domain 3, a nonsense mutation in the 5th LRR, and a nonsense mutation in the C terminus following the LRRs that causes a small deletion of the C terminus. These findings provide evidence that NB domain 3 and the C terminus are required for full activity of the plant R gene. They also suggest that alterations of the resistance gene can cause major differences in pathogen specificity by affecting interactions with an avirulence factor.

• The Korean Journal of Physiology and Pharmacology
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• 제17권6호
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• pp.525-530
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• 2013

Multidrug resistance 3 (MDR3) is expressed on the canalicular membrane of the hepatocytes and plays an important role in protecting the liver from bile acids. Altered ABCB4 gene expression can lead to a rare hepatic disease, low phospholipid-associated cholelithiasis (LPAC). In this study, we characterized 3 ABCB4 mutations in LPAC patients using various in vitro assay systems. We first measured the ability of each mutant to transport paclitaxel and then the mechanisms by which these mutations might change MDR3 transport activity were determined using immunoblotting, cell surface protein biotinylation, and immunofluorescence. Through a membrane vesicular transport assay, we observed that the uptake of paclitaxel was significantly reduced in membrane vesicles expressing 2 ABCB4 mutations, F165I and S320F. Both mutants showed significantly decreased total and cell surface MDR3 expression. These data suggest two missense mutations of ABCB4 may alter function of MDR3 and ultimately can be determined as LPAC-causing mutations.

• Molecules and Cells
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• 제39권10호
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• pp.722-727
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• 2016

Cardiomyopathy is a major cause of death worldwide. Based on pathohistological abnormalities and clinical manifestation, cardiomyopathies are categorized into several groups: hypertrophic, dilated, restricted, arrhythmogenic right ventricular, and unclassified. Dilated cardiomyopathy, which is characterized by dilation of the left ventricle and systolic dysfunction, is the most severe and prevalent form of cardiomyopathy and usually requires heart transplantation. Its etiology remains unclear. Recent genetic studies of single gene mutations have provided significant insights into the complex processes of cardiac dysfunction. To date, over 40 genes have been demonstrated to contribute to dilated cardiomyopathy. With advances in genetic screening techniques, novel genes associated with this disease are continuously being identified. The respective gene products can be classified into several functional groups such as sarcomere proteins, structural proteins, ion channels, and nuclear envelope proteins. Nuclear envelope proteins are emerging as potential molecular targets in dilated cardiomyopathy. Because they are not directly associated with contractile force generation and transmission, the molecular pathways through which these proteins cause cardiac muscle disorder remain unclear. However, nuclear envelope proteins are involved in many essential cellular processes. Therefore, integrating apparently distinct cellular processes is of great interest in elucidating the etiology of dilated cardiomyopathy. In this mini review, we summarize the genetic factors associated with dilated cardiomyopathy and discuss their cellular functions.

• Molecules and Cells
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• 제20권2호
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• pp.228-234
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• 2005

Caenorhabditis elegans him-6 mutants, which show a high incidence of males and partial embryonic lethality, are defective in the orthologue of human Bloom's syndrome protein (BLM). When strain him-6(e1104) containing a missense him-6 mutation was irradiated with ${\gamma}$-rays during germ cell development or embryogenesis, embryonic lethality was higher than in the wild type, suggesting a critical function of the wild type gene in mitotic and pachytene stage germ cells as well as in early embryos. Even in the absence of ${\gamma}$-irradiation, apoptosis was elevated in the germ cells of the him-6 strain and this increase was dependent on a functional p53 homologue (CEP-1), suggesting that spontaneous DNA damage accumulates due to him-6 deficiency. However, induction of germline apoptosis by ionizing radiation was not significantly affected by the deficiency, indicating that HIM-6 has no role in the induction of apoptosis by exogenous DNA damage. We conclude that the C. elegans BLM orthologue is involved in DNA repair in promeiotic cells undergoing homologous recombination, as well as in actively dividing germline and somatic cells.