Genetic Analysis of MEFV Gene Pyrin Domain in Patients With Behçet's Disease

Objectives. Behçet's disease (BD) is a systemic vasculitis with recurrent oral and genital ulcers and uveitis. MEFV gene, which is the main factor in familial Mediterranean fever (FMF), is also reported to be a susceptibility gene for BD. The pyrin domain of MEFV gene is a member of death-domain superfamily and has been proposed to regulate inflammatory signaling in myeloid cells. This study was designed to determine if mutations in pyrin domain of MEFV gene are involved in BD. Methods. We analyzed the pyrin domain of MEFV gene in 54 Turkish patients with BD by PCR-analysis and direct sequencing. Results. Neither deletion or insertion mutations nor point mutations in pyrin domain were found in any patient. Conclusion. Although pyrin gene mutations have been reported in patients with BD, pyrin domain is not mutated. However, alterations in other regions of MEFV gene and interaction between pyrin domains are needed to be further investigated

STUB1 polyadenylation signal variant AACAAA does not affect polyadenylation but decreases STUB1 translation causing SCAR16

We present three siblings afflicted with a disease characterized by cerebellar ataxia, cerebellar atrophy, pyramidal tract damage with increased lower limb tendon reflexes, and onset of 31 to 57 years, which is not typical for a known disease. In a region of shared homozygosity in patients, exome sequencing revealed novel homozygous c.*240T>C variant in the 3'UTR of STUB1, the gene responsible for autosomal recessive spinocerebellar ataxia 16 (SCAR16). In other genes, such an alteration of the evolutionarily highly conserved polyadenylation signal from AATAAA to AACAAA is known to highly impair polyadenylation. In contrast, RNA sequencing and quantification revealed that neither polyadenylation nor stability of STUB1 mRNA is affected. In silico analysis predicted that the secondary structure of the mRNA is altered. We propose that this change underlies the extremely low amounts of the encoded protein in patient leukocytes

IVSII-74 T > G: As harmless as we thought?

Background: IVSII-74 T > G is one of the most frequently identified polymorphic sites on the beta-globin gene. In our report, we present three cases with low mean corpuscular volume (MCV) value in three and high red blood cell (RBC) value in two of the cases. The objective of this study was to further analyse the reason for condition of three patients, who were referred for the investigation of persistent anemia

Tumor microsatellite instability and clinical outcome in patients with colorectal cancer

30th Congress of the European-Society-for-Medical-Oncology -- SEP 29-OCT 03, 2006 -- Istanbul, TURKEYWOS: 000248078900857…European Soc Med Onco

Association of NFKB1 and NFKBIA Polymorphisms in Relation to Susceptibility of Behcet's Disease

Behcet's disease (BD) is a chronic inflammatory autoimmune disease. Although raised levels of proinflammatory cytokines in BD have been reported, the pathogenesis is still unknown. The aim of this study was to investigate the association of NFKB1 and NFKBIA polymorphisms and their single and combined analysis effects on susceptibility of BD in Turkish population. We analysed the distribution of NFKB1 -94 ins/del ATTG (rs28362491) and NFKBIA 3 UTR AG (rs696) polymorphisms using PCR-RFLP method in 89 patients with BD and 190 controls in this population. Statistical analysis of the results was performed by calculating OR, and 95% CI via (2) test and using Bonferroni correction. According to the significant results of both single and combined genotype analysis, the frequencies of ins/ins genotype and ins allele of rs28362491 were significantly higher in patients with BD (Pc=0.003, 0.004, respectively). Also, higher frequencies of the rs696 variant containing AA genotype was found in patients with BD (Pc=0.0033), whereas no statistical significant differences in distribution of the alleles of rs696 polymorphism in patients and controls. In addition, according to the combined genotype analysis, the wild type of both rs28362491 and rs696 polymorphisms (ins/ins/AA genotype) was also significantly higher in BD cases (Pc=0.044). Our findings prove that both single and combined genotype analysis of rs28362491 and rs696 polymorphisms indicate that the wild genotypes of both two SNPs (ins/ins and AA genotypes) and ins/ins/AA combined genotype are strongly associated with enhanced risk of BD in a Turkish population