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Neishabury M.,University of Social Welfare and Rehabilitation Sciences | Oberkanins C.,ViennaLab Diagnostics GmbH | Abedini S.S.,University of Social Welfare and Rehabilitation Sciences | Zamani S.,University of Social Welfare and Rehabilitation Sciences | And 2 more authors.
Blood Cells, Molecules, and Diseases | Year: 2011

Our data on 114 Iranian individuals with thalassemia intermedia phenotype revealed homozygous or compound heterozygous beta-globin mutations to be the predominant disease factor in 86.2% of cases. However, 8.2% of these individuals were found to be heterozygous or wild type for beta-globin mutations. In search for determinants outside of the beta-globin gene, which could be responsible for the unexpected thalassemia intermedia phenotype in these subjects, we screened the alpha-globin genes, the 5'HS3 and 5'HS4 regions of the beta-globin LCR, and the NF-E2 transcription factor for sequence variations in selected individuals. The -3.7 deletion was the only alpha-globin mutation detected, and no alterations were found in 5'HS3 and NF-E2. Sequence analysis of the 5'HS4 LCR core region identified three known SNPs in a single patient, who required irregular blood transfusions. The A/G polymorphism in the 5'HS4 palindromic region was also observed to be variable. Family studies were carried out on a female G/G homozygous patient, who received irregular blood transfusions. Her father, who had the same heterozygous IVSII-1 beta-globin mutation but the A/G genotype at the 5'HS4 palindromic site, presented with mild anemia and no requirement for blood transfusions. This suggests an impact of SNPs in the 5'HS4 LCR core region on the thalassemia phenotype and offers an interesting subject for further investigations in the Iranian population. © 2010 Elsevier Inc.


van Trotsenburg M.,University of Amsterdam | Oberkanins C.,ViennaLab Diagnostics GmbH | Atamaniuk J.,Institute of Laboratory Diagnostics
Journal of Clinical Laboratory Analysis | Year: 2013

Background: We have already described a significantly elevated overall risk for recurrent pregnancy loss (RPL) in women carrying the coagulation factor XIII (FXIII) Val34Leu and/or the plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism assuming that these polymorphisms contribute synergistically to RPL because of impaired hypofibrinolysis. Recent studies on FXIII indicate that the impact of the FXIII 34Leu genotype on fibrin structure and fibrinolysis is affected by fibrinogen concentration. Therefore, we reinvestigated the association between fibrinogen concentrations and FXIII Val34Leu with early RPL. Materials and Methods: In this case-control study, we enrolled 49 women with a history of two consecutive or three to six nonconsecutive pregnancy losses between the 8th and 12th week of gestation and 48 healthy controls. The risk for RPL in carriers of FXIII 34Leu at fibrinogen levels above or below the median and first tertile of controls was evaluated. Results: In carriers of the 34Leu allele, fibrinogen levels below the median (i.e., ≤300 mg/dl) and the first tertile (i.e., ≤284 mg/dl) of controls were associated with an increased risk for RPL [(2.9 (1.1-7.7), 3.9(1.0-15.0)]. Conclusions: The FXIII Val34Leu polymorphism may be associated with the development of early RPL in association with fibrinogen concentrations. At fibrinogen levels in the low normal range, FXIII 34Leu may modify fibrin structure toward an increased resistance to fibrinolysis. © 2013 Wiley Periodicals, Inc.


Saroufim M.,American University of Beirut | Novy M.,ViennaLab Diagnostics GmbH | Taraif S.,Saad Specialist Hospital | Habib R.H.,American University of Beirut | And 5 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2014

Background Proto-oncogene B-Raf (BRAF) mutation rates have been reported in nevi and melanomas of homogeneous Caucasian cohorts. Objective To study the demographics of BRAF mutations in dysplastic nevi of populations with differing potential solar UV radiation exposure. Methods Extended BRAF testing for 9 mutations in 125 dysplastic nevi from 101 patients, derived from populations with differing potential UV radiation exposure rates (Lebanon and Saudi Arabia), was performed. Clinical and microscopic parameters were recorded. Results BRAF mutation status was carried out for 101/125 (80.8%) cases with an overall mutation rate of 62.4% (63/101). V600E (c.1799T > A) was the predominant mutation, found in 61/63 (96.8%) cases. BRAF mutation rate differed significantly by potential UV radiation exposure (Lebanon: 53.4%, Saudi Arabia: 74.4%, P < 0.05). A 43.8% discordant mutation rate (7/16 patients) was found in patients with multiple nevi, including 2 patients with different BRAF mutations. Microscopic examination subdivided the dysplasia into mild (n = 24), moderate (n = 60) and severe (n = 41) with trunk predominance (72.8%). Higher rates of pigment in the stratum corneum were identified in Saudi Arabia (P < 0.05). No statistical significant increase in BRAF mutation rate was noted with advanced architectural and cytological atypia. Parameters associated with a negative BRAF mutation status included upper extremity location, regression, cohesiveness and presence of suprabasal melanocytes (P < 0.05). Positive BRAF mutation status was reasonably predicted by multivariate binary logistic regression by 2 independent predictors: Geographic location and compound nevus type. Conclusions In our Near Eastern cohort, the BRAF mutation rate varied significantly by geographic location. In patients with multiple dysplastic nevi examined, discordant BRAF mutation status potentially negates an underlying constitutional predilection. © 2013 European Academy of Dermatology and Venereology.


Kriegshuser G.,ViennaLab Diagnostics GmbH | Auner V.,Ludwig Boltzmann Institute for Gynecological Oncology and Reproductive Medicine | Zeillinger R.,ViennaLab Diagnostics GmbH
Expert Opinion on Medical Diagnostics | Year: 2010

Importance of the field: KRAS mutation is the most common oncogenic alteration in various human cancers. Recently, KRAS has emerged as an important predictive biomarker in common malignancies such as metastatic colorectal cancer (mCRC) and non-small cell lung cancer (NSCLC). This work aims to discuss the clinical impact of the KRAS mutation status on state-of-the-art treatment approaches, including epidermal growth factor receptor (EGFR)-targeted therapies. Areas covered in this review: This review considers the potential of KRAS to serve as a diagnostic, prognostic or predictive biomarker in various cancers, including those of the lung, colon/rectum, pancreas, ovary and endometrium. What the reader will gain: KRAS mutations in mCRC and NSCLC primary tumors predict resistance to EGFR-targeted therapy. In pancreatic cancer, KRAS may prove useful as a diagnostic biomarker to screen for early neoplasia. Furthermore, quantitative KRAS mutation analysis could have the potential to distinguish pancreatic cancer from other conditions such as chronic pancreatitis. With respect to ovarian and endometrial cancer, further studies should focus on determining reliable biomarkers for predicting response to EGFR-targeted therapy. Besides EGFR inhibition, KRAS may also serve as a diagnostic and predictive biomarker for evolving therapies directed against mutant RAS proteins. Take home message: KRAS has been recognized as an outstanding predictive biomarker to select mCRC and NSCLC patients for EGFR-targeted therapies; however, multi-determinant approaches including other molecular markers should facilitate the identification of patients likely to respond to such therapies. © 2010 Informa UK, Ltd.


Al-Allawi N.A.S.,Duhok University | Puehringer H.,ViennaLab Diagnostics GmbH | Raheem R.A.,Hereditary Anemia Center | Oberkanins C.,ViennaLab Diagnostics GmbH
Genetic Testing and Molecular Biomarkers | Year: 2015

To determine the molecular basis of β-thalassemia intermedia (TI) and the contribution of the three hemoglobin F (HbF) quantitative trait loci (QTLs) on chromosomes 11, 2, and 6 to the milder phenotype, a total of 102 Iraqi Arab patients with TI were studied. The β and α genotypes as well as HBG2?g. 158 C>T (rs7482144), BCL11A (rs1427407 and rs10189857), and HBS1L-MYB (rs28384513 and rs9399137) by multiplex polymerase chain reaction and reverse hybridization were studied. A total of 21 different β-thalassemia mutations arranged in 35 different genotypes were identified. The genotypes encompassed β+/β+ mutations in 33 cases, β+/β0 in 17 cases, β0/β0 in 47 cases, β0/wild type in 3 and β0/Hb E in 2 cases. The most common was IVS-II-1 (G>A)/IVS-II-1 (G>A), followed by IVS-I-6 (T>C)/IVS-I-6 (T>C) and IVS-I-110 (G>A)/IVS-I-110 (G>A), in 31.4%, 17.6%, and 6.9%, respectively. Alpha-thalassemia mutations were found in 15.2% of those homozygous for the β-mutations, while α gene triplication was identified in all three heterozygotes. Of the five QTLs tested, only rs7482144 and rs10189857 were significantly associated with β0/β0 when compared to β+/β+, with odds ratios of 6.4 (95% confidence interval [CI] 2.9-14.0) and 3.2 (95% CI 1.2-8.6), respectively. In conclusion, this study has demonstrated that among Iraqi patients with thal intermedia, the main contributors to the milder phenotype were β+ alleles, XmnI polymorphism, and BCL11A (rs10189857), while other QTLs on chromosomes 2 and 6, as well as alpha-thalassemia, were not significantly relevant. © 2015, Mary Ann Liebert, Inc.

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