[Show abstract][Hide abstract] ABSTRACT: gouty arthritis and familial Mediterranean fever (FMF) share some clinical and pathological features such as being classified as auto inflammatory disease, association with inflammasome, short‐lived intermittent arthritis, and good response to colchicine and anti‐interleukin‐1 treatments. As Mediterranean fever (MEFV) gene is the causative factor of FMF, we aimed to investigate the prevalence of MEFV gene mutations and their effect on disease manifestations in Turkish gouty arthritis patients.Methodsninety‐seven patients diagnosed with primary gouty arthritis (93 M and 4 F, 54 [37‐84] years) and 100 healthy controls (94 M and 6 F, 57 [37‐86] years) included in the study. All subjects were genotyped for the MEFV variations. Number of gout attacks, diuretic use, and history of nephrolithiasis and presence of tophus were also recordedResultsthe carriage rate of MEFV mutations for patients and controls were 22.7% (n = 22) and 24% (n = 24) respectively. The comparison of the patient and control groups yielded no significant difference in terms of the MEFV mutations carriage rate (p = 0.87). The allelic frequencies of the MEFV mutations in patients were 11.9% (n = 23) and 14% (n = 28) in controls (p = 0.55). The presence of MEFV variants did not show any association with clinical features of gouty arthritis. The subgroup analysis of patients revealed that gouty arthritis patients with mutations had similar frequencies of tophus, history of nephrolithiasis and podogra compared to the ones without mutations (p > 0.05).Conclusionsthis study does not provide support for a major role of MEFV mutations in Turkish gouty arthritis patients.
Revista Brasileira de Reumatologia 11/2014; · 0.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Liver-derived paraoxonase-1 (PON1) enzyme that is found in the circulation is bound to high-density lipoproteins and reduces the amount of oxidized lipids with its antioxidant effect. Humans have at least three different PON gene regions which are adjacent to the other on the 7th chromosome. It has been shown that PON1 gene and its polymorphisms are related with various diseases. It is also known that, hepatitis C virus (HCV) is tightly associated with the cell lipoproteins in each step of its replication cycle leading to modulation of the host lipid metabolism. The aim of this study was to investigate the relationship between the response to chronic hepatitis C (CHC) therapy and aminoacid changes in 55' and 192' regions of PON1 enzyme believed to be involved in the pathophysiology of many chronic diseases. A total of 49 CHC patients (27 male, 22 female; mean age: 52.9 ± 12.6 yrs), all infected with HCV genotype 1b and positive for anti-HCV and HCV-RNA were included in the study. Patients who were HCV-RNA negative at the sixth month following at least once pegilated interferon + ribavirin treatment, were considered as therapy-responders, whereas those who were HCV-RNA positive were considered as non-responders. The genomic DNAs were isolated from patients' blood samples in their routine follow-ups and Q/R192 and L/M55 PON1 polymorphism analysis in 55. and 192. regions was performed by T-ARMS-PCR (Tetra-primer amplification refractory mutation system-polymerase chain reaction) method. In our study, the analysis of PON1 polymorphisms yielded 44.1% of LL, 44.1% of LM and 11.8% of MM genotypes at position 55 and 55.9% of QQ, 41.2% of QR, and 2.9% of RR genotypes at position 192 in therapy-responders. In the evaluation of combined genotype analysis of the patients, there was only one case who was responsive to treatment with LL/RR genotype. Of the patients, eight harbored LL/QQ genotypes and seven of them (87.5%) were responsive to treatment. However, statistical analysis indicated that there was no relationship between PON1 L/M55 and PON Q/R192 polymorphisms and response to CHC treatment (chi-square test, p> 0.05). Our data did not support a relationship between PON1 polymorphisms and response to CHC therapy, in contrast to a few studies pointing out of this correlation. This might be attributed to relatively low number of patients included. In conclusion, since antiviral agents used for CHC therapy are limited and costly, it was thought that further investigations with large numbers of patients should be conducted to establish the presence of any relationship between the response to CHC therapy and genotypes of the PON1 enzyme.
[Show abstract][Hide abstract] ABSTRACT: Background
In general, medical geneticists aim to pre-diagnose underlying syndromes based on facial features before performing cytological or molecular analyses where a genotype–phenotype interrelation is possible. However, determining correct genotype–phenotype interrelationships among many syndromes is tedious and labor-intensive, especially for extremely rare syndromes. Thus, a computer-aided system for pre-diagnosis can facilitate effective and efficient decision support, particularly when few similar cases are available, or in remote rural districts where diagnostic knowledge of syndromes is not readily available.
The proposed methodology, visual diagnostic decision support system (visual diagnostic DSS), employs machine learning (ML) algorithms and digital image processing techniques in a hybrid approach for automated diagnosis in medical genetics. This approach uses facial features in reference images of disorders to identify visual genotype–phenotype interrelationships. Our statistical method describes facial image data as principal component features and diagnoses syndromes using these features.
The proposed system was trained using a real dataset of previously published face images of subjects with syndromes, which provided accurate diagnostic information. The method was tested using a leave-one-out cross-validation scheme with 15 different syndromes, each of comprised 5–9 cases, i.e., 92 cases in total. An accuracy rate of 83% was achieved using this automated diagnosis technique, which was statistically significant (p<0.01). Furthermore, the sensitivity and specificity values were 0.857 and 0.870, respectively.
Our results show that the accurate classification of syndromes is feasible using ML techniques. Thus, a large number of syndromes with characteristic facial anomaly patterns could be diagnosed with similar diagnostic DSSs to that described in the present study, i.e., visual diagnostic DSS, thereby demonstrating the benefits of using hybrid image processing and ML-based computer-aided diagnostics for identifying facial phenotypes.
Artificial Intelligence in Medicine 08/2014; · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic arthritis of familial Mediterranean fever (FMF) involves weight-bearing joints and can occur in patients without a history of acute attack. Our aim was to investigate a possible causal relationship between FMF and osteoarthritis in a population in which FMF is quite common.
Patients with late stage primary osteoarthritis were enrolled, and five MEFV gene mutations were investigated. The frequency of MEFV gene mutations was compared among patients with osteoarthritis and a previous healthy group from our center.
One hundred patients with primary osteoarthritis and 100 healthy controls were studied. The frequency of MEFV gene mutations was significantly lower in the osteoarthritis group (9% vs. 19%). M694V was the most frequent mutation (5%) in the osteoarthritis group, whereas in the control group, E148Q was the most common (16%). In subgroup analyses, the mutation frequency of patients with hip osteoarthritis was not different from that of patients with knee osteoarthritis and controls (7.1%, 9.7%, and 19%, respectively). There were no differences among the three groups with respect to MEFV gene mutations other than E148Q (8.1% vs. 3.6%). E148Q was significantly lower in the osteoarthritis group than in the controls (16% vs. 1%), although the mutations did not differ between patients with knee osteoarthritis and controls.
In a population with a high prevalence of MEFV gene mutations, we did not find an increased mutation rate in patients with primary osteoarthritis. Furthermore, we found that some mutations were significantly less frequent in patients with osteoarthritis. Although the number of patients studied was insufficient to claim that E148Q gene mutation protects against osteoarthritis, the potential of this gene merits further investigation.
The Korean Journal of Internal Medicine 09/2013; 28(5):594-8.
[Show abstract][Hide abstract] ABSTRACT: We assessed the role played by the ERAP1 gene in Turkish patients with ankylosing spondylitis (AS) in terms of disease susceptibility, clinical manifestations, and disease severity. We included 150 consecutive AS patients who met the modified New York classification criteria and 150 healthy controls. We documented the presence of 10 ERAP1 single-nucleotide polymorphisms (SNPs) and HLA-B27 in these patients. ERAP1 SNPs were genotyped using competitive allele-specific polymerase chain reaction. Differences between genotype and allele frequencies were compared using the Pearson's Chi-square test. The associations between ERAP1 SNPs, on the one hand, and with disease severity and clinical findings, on the other, were determined. One SNP, rs26653, was significantly associated with AS susceptibility (OR 1.609, 95 % CI 1.163-2.226; p = 0.004). The population-attributable risk of possession of the rs26653 SNP allele was 23.4 %. No relationship was noted between HLA-B27 positivity and the distribution of rs26653 genotype frequency. No associations were seen between disease severity measures and clinical manifestations of AS. In summary, an ERAP1 polymorphism was associated with AS in a Turkish population. The contributions of HLA-B27 and the rs26653 SNP to AS pathogenesis appear to be independent.
Rheumatology International 07/2013; · 1.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction: Deep venous thrombosis and pulmonary embolism, known as venous thromboembolism and seen as a fairly common multifactorial diseases. Differ between populations due to genetic factors, several polymorphisms associated with venous thromboembolism was conducted. As a result of these studies the relationship between disease development and polymorphism is not clear yet. In this study we aimed to investigate the role of angiotensin converting enzyme insersion/deletion (ACE I/D) and plasminogen activator inhibitor-1 4G/5G (PAI-1 4G/5G) polymorphism in the development of disease. Materials and Methods: In our study, DNA isolated from 80 venous thromboembolism patients and 79 control groups was used. While the classical polymerase chain reaction method used to investigate the ACE I/D polymorphism, the polymerase chain reaction based on allele-specific amplification was used for the detection of PAI-1 4G/5G polymorphism. Results: As a result, there were no significant statistical differences for ACE I/D and PAI-1 4G/5G polymorphism among patient and control groups (p> 0.05). Conclusion: These findings revealed that there is no relationship between these polymorphisms and the development of venous thromboembolism, but large-scale studies are need to be done.
[Show abstract][Hide abstract] ABSTRACT: The study investigated whether travelling after amniocentesis has an effect on outcomes of the procedure. A total of 57 patients who were referred to our tertiary centre from distant cities and who had to travel back by bus, by car or by plane, were evaluated for amniocentesis outcomes. The travelled distances were divided into 3 zones, which consisted of 50-100, 101-300 and over 300 km. Patients (n = 85) residing in our city (within 50 km) were identified as the control group. All of the procedures were done by the same perinatology team, following exactly the same procedure. It was found that there was one transient amniotic fluid leakage patient who had travelled 70 km by car after the amniocentesis. No other patients who had to travel after amniocentesis had a complication related to the procedure. It was concluded that although done on a limited number of patients, this study provides the first scientifically supported evidence that travelling by bus, by car or by plane after amniocentesis does not have adverse effects on the outcomes.
Journal of Obstetrics and Gynaecology 05/2013; 33(4):343-5. · 0.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The coincidence of trisomy 21 and a structural rearrangement is very rare, and even it has not been reported as a prenatal diagnosis yet. In this article, we present an autosomal translocation carrier fetus with trisomy 21: 47,XX,+21, t(3;8)(p21;q24). Although the coincidence of reciprocal translocation and trisomy may be seen in reciprocal translocation carrier families, de novo cases are extremely rare. The presented case is diagnosed by amniocentesis, which was performed because of abnormal fetal ultrasonographic findings and increased trisomy 21 risk at maternal serum screening test. The postmortem pathologic examination of the fetus revealed that the findings of hypertelorism and right lung with two lobes are interesting novel findings of our cases associated with the breakpoints 3p21 and 8q24.
Fetal and pediatric pathology 01/2013; · 0.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the clinical diagnosis of facial dysmorphology, geneticists attempt to identify the underlying syndromes by associating facial features before cyto or molecular techniques are explored. Specifying genotype-phenotype correlations correctly among many syndromes is labor intensive especially for very rare diseases. The use of a computer based prediagnosis system can offer effective decision support particularly when only very few previous examples exist or in a remote environment where expert knowledge is not readily accessible. In this work we develop and demonstrate that accurate classification of dysmorphic faces is feasible by image processing of two dimensional face images. We test the proposed system on real patient image data by constructing a dataset of dysmorphic faces published in scholarly journals, hence having accurate diagnostic information about the syndrome. Our statistical methodology represents facial image data in terms of principal component analysis (PCA) and a leave one out evaluation scheme to quantify accuracy. The methodology has been tested with 15 syndromes including 75 cases, 5 examples per syndrome. A diagnosis success rate of 79% has been established. It can be concluded that a great number of syndromes indicating a characteristic pattern of facial anomalies can be typically diagnosed by employing computer-assisted machine learning algorithms since a face develops under the influence of many genes, particularly the genes causing syndromes.
Machine Learning and Applications (ICMLA), 2012 11th International Conference on; 01/2012
[Show abstract][Hide abstract] ABSTRACT: Ring chromosome 21 syndrome is a rare clinical condition. Most of the patients have a recognizable phenotype and multisystem involvement is described. Structural neurologic anomalies have also been described, but waddling gait due to lower motor neuron involvement has not been previously reported in association with ring 21.
Brain & development 12/2011; 34(9):792-5. · 1.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the rate of MEFV gene mutations, the gene responsible for familial Mediterranean fever (FMF), in patients with hematolymphoid neoplasm. The rate of the five most common MEFV gene mutations (M694V, M680I, V726A, M694I and E148Q) was determined in 46 patients with hematolymphoid neoplasm. We found a high frequency of carriers in patients with multiple myeloma (60%) and acute lymphocytic leukaemia (33.3%), whereas patients with chronic lymphocytic leukaemia (9%) and non-Hodgkin lymphoma (5%) had a low mutation carrier rate. There is no MEFV gene mutation in patients with Hodgkin lymphoma. Furthermore, the statistically significant predominance of strong heterozygous mutations such as M694V and M680I in patients with hematolymphoid neoplasm; none had own and/or family history compatible with FMF, is interesting. In conclusion, we found a high frequency of carriers for MEFV gene in patients with multiple myeloma and acute lymphocytic leukaemia. The data of our study may provide some new insights in understanding of individual genetic differences in susceptibility to these neoplasms.
International Journal of Immunogenetics 10/2010; 37(5):387-91. · 1.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to investigate the rate of MEFV, the gene mutated in familial Mediterranean fever, mutations in patients with myeloid neoplasm and to determine if known mutations of MEFV cause a tendency for myeloid neoplasms. The frequency of the five most common MEFV gene mutations (M694V, M680I, V726A, E148Q and M694I) was determined in 26 patients with myeloid neoplasm. We identified 1 homozygous (E148Q/E148Q), 1 compound heterozygous (M694V/E148Q) and 5 heterozygous MEFV gene mutations; none had their own and/or family history compatible with familial Mediterranean fever. The mean overall mutation rate was 0.269. We found a high frequency of carriers in patients with myelodysplastic syndrome (66.6%), polycythemia vera (33.3%) and acute myeloid leukemia (28.6%). However, there was no MEFV gene mutation in patients with chronic myeloid leukemia. In conclusion, this study reports for the first time a possibly high prevalence of MEFV gene mutations in patients with myeloid neoplasm, especially myelodysplastic syndrome, polycythemia vera and acute myeloid leukemia. Our findings could open new perspectives for MEFV gene mutations in myeloid neoplasms and its association with tumor promotion. Further research is needed to determine the actual role of MEFV gene mutations in these malignancies.
International journal of hematology 06/2010; 91(5):758-61. · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, our aim was to investigate the prevalence of Mediterranean fever (MEFV) gene mutations in patients with ankylosing spondylitis (AS) and assessing their clinical significance. Ninety-five consecutive patients (12 women, 83 men) with active AS were included to the study. All patient's relevant clinical data were recorded at the beginning and patient assessment measures were performed. The frequency of the eight most common MEFV mutations: M694V, V726A, E148Q, M680I, M694I, P369S, F479L, and the R761H were determined. Genetic analysis was carried out by the NanoChip Molecular Genetics Workstation. NSAIDs were given to patients for treatment. The rate of MEFV mutations and their clinical significance were assessed. With regard to the MEFV mutation analysis, 30.5% of AS patients were found to have at least one mutation. The response rate to the NSAIDs (P=0.825) or frequency of patients having active disease (P=0.066) after the treatment, were not found different between the patients those have MEFV mutations and the patients those were non-carriers. Furthermore, no clinical and laboratory difference between MEFV mutation carriers and non-carriers were found. We think that although prevalence of MEFV mutations is significantly high in AS patients without clinical features of familial Mediterranean fever, its influence to the prognosis is less likely. Further investigations are needed to define the impact of MEFV mutations on the disease course of ankylosing spondylitis.
Rheumatology International 08/2008; 29(1):37-42. · 1.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The word “dermatoglyphics” indicates study of epidermal ridge configuration on palms, soles and fingertips. This investigation was aimed to analyze dermatoglyphic patterns in Klinefelter's syndrome (KS) patients. The study cohort consisted of 57 cases and 25 controls. The prints were taken by using the ink method. Fingertip patterns, triradial counts, a-t-d angle and a-b ridge count were studied. There were significant differences in radial loops and whorls (p<0.05), and there were very highly significant differences in arches (p<0.001) in KS patients as compared to controls. Dermatoglyphic patterns at the hypothenar area (p<0.05), and areas between at the I. interdigital and thenar sites (p<0.001) have been found to be significantly different in KS patients compared to controls. Total ridge counts (TRC), a-b, a-t-d angels were not different in the two groups (p>0.05). A definite correlation between the dermatoglyphic patterns and the KS has been shown.
[Show abstract][Hide abstract] ABSTRACT: Familial Mediterranean fever (FMF) is an autosomal-recessive disease. It is characterized by recurring fever, abdominal pain, and serositis. The Mediterranean fever (MEFV) gene is localized on 16p13.3 and more than 35 mutations have been described to date. There are some differences in the gene mutations of FMF in the various ethnic groups. The aim of this study is to determine the frequency of the mutations which has been reported comparatively rare, to define the most effective mutation set, and to select the most suitable DNA analysis system for Turkish FMF patients. Mutations in 330 Turkish FMF patients with typical phenotypes from various regions of Turkey were evaluated for the research purposes. These patients were analyzed for six MEFV gene mutations by the NanoChip Molecular Genetics Workstation. The most frequent mutation was M694V, identified in 50.00% of the alleles examined; M680I followed with 14.10% and V726A--9.70%. Consequently, we determined that R761H (n = 23; 3.48%) was the most frequent rare mutations in Turkish FMF patients. Frequency of the rare mutations were R761H (3.48%), E148Q (1.36%), and M694I (1.21%). All of these mutations were in the compound heterozygote state. Our study showed that R761H mutations were higher than it has been reported in literature until now and were mainly associated with M694V. We suggest that mutation R761H should be included in the mutation scanning analysis researches or considered if the patient has M694V/? mutation especially in Turkish FMF patients. Larger serial studies need to be done to investigate the rate and coexistence of these mutations.
[Show abstract][Hide abstract] ABSTRACT: Tricho-rhino-phalangeal syndrome (TRPS) is a rare and an autosomal dominant disorder having the following characteristics: slowly growing sparse hair, medially thick and laterally thin eyebrows, bulbous tip of the nose, long flat philtrum and thin upper lip with vermilion border, protruding ears, cone-shaped epiphyses and swelling. Our report intends to introduce TRPS to the dental literature and to present oral, clinical and radiological data of a patient with TRPS. A rare association of supernumerary teeth was also diagnosed and one of them was extracted as it impeded on the eruption path of left premolar tooth.
Journal of Indian Society of Pedodontics and Preventive Dentistry 04/2007; 25(1):43-5.