1,721,035 research outputs found
A New Biomarker on Bone Resorption in Chronic Otitis Media: Osteoprotegerin and NLRP3 Inflammasome Gene Polymorphisms
No full textChronic Otitis Media (COM) is a chronic inflammation of the middle ear and mastoid with persistent membrane perforation and hearing loss. Osteoprotegerin (OPG) and NOD like receptor protein 3 (NLRP3) play an important role in bone metabolism. The aim of the study was to investigate the role of OPG and NLRP3 gene polymorphism on ossicular chain resorption in COM. Fourty COM patients and 20 healhty control group were included in the study. While 20 patients underwent ossiculoplasty, 20 patients underwent type 1 tympanoplasty. DNA was isolated from peripheral blood using the DNA kit. OPG gene c.226A > C (p.Thr76Pro) and NLRP3 gene c.592G > A (p. Val198Met) polymorphisms were genotyped using melting curve analysis technique. NLRP3 gene polymorphism were determined in 6 of 20 patients (30%) in ossiculoplasty group, 4 of 20 patients (20%) in type 1 tympanoplasty group and 3 of 20 patients (15%) in control group. OPG gene polymorphism were determined in 5 of 20 patients (25%) in ossiculoplasty group, 3 of 20 patients (15%) in type 1 tympanoplasty group and 1 of 20 patients (5%) in control group, respectively. There was no statistically significant difference between groups regarding to results. Although the difference was not significant NLRP3 and OPG gene polymorphisms were higher in the ossiculoplasty group. Since NLRP3 and OPG gene polymorphisms were determined to be higher numerically in the ossiculoplasty group, OPG and NLRP3 gene regulation system may have an effect on ossicular chain destruction in COM
Comparison of the Treatment Efficacy of Rituximab and Plasmapheresis/Intravenous Immunoglobulin Combination with Historical Control in Chronic Antibody Mediated Rejection
No full textOBJECTIVE: Chronic antibody mediated rejection (CAMR) is a major therapeutic challenge for achieving long-term graft survival; treatment options are limited to several anti-humoral interventions. MATERIAL and METHODS: Efficacy of rituximab combination therapy was retrospectively investigated by comparison with a historical control group for allograft function at six month and overall graft survival/dysfunction. The inclusion criterion was biopsy proven chronic AMR according to the Banff 2007 classification. Nineteen patients found eligible, rituximab group had nine patients (rituximab, plasmapheresis and low dose IVIG); control group had ten recipients. Predictive factors for graft failure also investigated according to Banff scores and renal functions. RESULTS: None of the outcomes were exposed significant efficacy of rituximab, although better treatment response at sixth month (55% vs. 40%, p= 0.51), fewer overall graft failures (33% vs. 60%, p= 0.25) and dysfunctions (66% vs. 80%, p= 0.52). Overall, 47% of patients suffered graft failure. Advanced transplant glomerulopathy was found in 90% of biopsies (all scored = 2). Peritubular capillaritis score (1.67 +/- 0.87 vs. 0.70 +/- 0.94, p= 0.04) and interstitial inflammation score (1.78 +/- 0.44 vs. 1.00 +/- 0.47, p= 0.004) were significantly higher in recipients who suffered graft failure. CONCLUSION: Rituximab could not sufficiently prevent further deterioration of allograft and failed to improve allograft survival in CAMR, especially after settlement of the irreversible transplant glomerulopathy
Association between occurrence of ossicular chain defect and osteoprotegerin gene expression in patients with chronic otitis media
No full textObjective Chronic otitis media (COM) is an important debilitating public problem causing hearing loss due to irreversible resorption of the ossicular chain. Activation of osteoprotegerin (OPG) during an acute attack of COM prevents bone resorption. The aim of the study was to investigate the role of OPG gene expression level on ossicular chain resorption in chronic otitis media. Materials and methods Fifty operated COM patients were included in the study. While 20 patients underwent ossiculoplasty, 30 patients underwent type 1 tympanoplasty. For RNA isolation and OPG gene expression analysis, middle ear swabs were taken from nasopharynx in the ostium of the Eustachian tube. RNA was isolated with mRNA easy kit and kept at - 85 degrees C till the cDNA and expression analysis. Expression levels were analyzed with real-time quantitative PCR in comparison with PDGB gene expression level as an internal control. Results Sample Cq measurements of type 1 tympanoplasty group were higher than Cq measurements of the internal control group (p = 0.027; p < 0.05). In contrast, there was no statistically significant difference between sample Cq measurements of ossiculoplasty group and Cq measurements of the internal control group (p = 0.293; p > 0.05). Conclusion Since OPG gene expression level was significantly higher in type 1 tympanoplasty group, OPG gene regulation system may have an effect on ossicular chain destruction in COM
The GABA(A) Receptor gamma 2 Subunit (R43Q) Mutation in Febrile Seizures
No full textBACKGROUND: Febrile seizure is the most common form of childhood seizure. Although its exact cause is unclear, many researchers emphasize the importance of its genetic predisposition. Recent genetic studies revealed the importance of the mutations of the gamma-aminobutyric acid A receptor as the etiology of the febrile seizures. R43Q mutation affecting the gamma 2-subunit N-terminal domain has been related to childhood absence epilepsy and febrile seizure. METHODS: We investigated R43Q mutations of the GABRG2 gene, located on the long arm of chromosome 5 encoding the gamma 2-subunit of the gamma-aminobutyric acid A receptor. We studied 44 patients with febrile seizure and 49 children without any febrile seizure who were admitted to our clinic. RESULTS: We found that 36% of our patient group, the children who experienced febrile convulsions, had heterozygous R43Q mutation. Statistical studies revealed that heterozygous R43Q mutation of gamma-aminobutyric acid A receptor gamma 2 subunit was higher in the study group than in the control group (P < 0.01). CONCLUSIONS: Heterozygous gamma-aminobutyric acid A receptor gamma 2 subunit (R43Q) mutation may have an effect in the development of febrile seizures
The Spectrum of Low-Density Lipoprotein Receptor Mutations in a Large Turkish Cohort of Patients with Familial Hypercholesterolemia
No full textBackground: Monogenic hypercholesterolemia with Mendelian inheritance is a heterogeneous group of diseases that are characterized by elevated plasma low-density lipoprotein cholesterol (LDL-C) levels, and the most common form of this disorder is autosomal-dominant familial hypercholesterolemia (FH). Methods: A total of 104 index cases with the clinical diagnosis of FH were included in this study. Low-density lipoprotein receptor (LDLR) was sequenced using the Sanger sequencing method. Results: Pathogenic/likely pathogenic variants were detected in LDLR in 55 of the 104 cases (mutation detection rate = 52.8%). Thirty different variants were detected in LDLR, three of which were novel. The total cholesterol and LDL-C values of the patients in the group of premature termination codon (PTC) mutation carriers were significantly higher than those of the patients in the group of non-PTC mutation carriers. A total of 87 patients (17 pediatric and 70 adult cases) were diagnosed with cascade genetic screening. Statin treatment was recommended to all 87 patients and was accepted and initiated in 70 of these patients. Conclusions: This study is the largest patient cohort that evaluated FH cases in the Turkish population. Herein, we revealed the LDLR mutation spectrum for a Turkish population and compared the cases in the context of genotype-phenotype correlation. Genetic screening of individuals with suspected FH not only helps to establish their diagnosis, but also facilitates early diagnosis and treatment initiation in other family members through cascade screening
A large Turkish pedigree with multiple endocrine neoplasia type 1 syndrome carrying a rare mutation: c.1680_1683 del TGAG
No full textBackground/Aims: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized by tumors arising from endocrine glands with no specific genotype-phenotype correlation. Here, we report the largest Turkish kindred with MEN1 syndrome which inherited a scarce MEN1 mutation gene. Materials and Methods: A 64-year-old man, referred to our gastroenterology outpatient clinic for evaluation of a pancreatic mass lesion, was diagnosed with MEN1 syndrome after endoscopic ultrasound-guided sampling of the mass revealed pancreatic neuroendocrine tumor (pNET) and accompanying primary hyperparathyroidism (PHPT) and pituitary tumor. Genetic analysis by whole gene Sanger sequencing of the MEN1 gene identified a frame-shift mutation in exon 10 (c.1680_1683delTGAG). All the relatives of the index case were proposed for clinical and genetic evaluation for MEN1 syndrome. Results: Of the 25 relatives of the index case, 17 were diagnosed with the MEN1 syndrome. Eighteen members among all relatives consented to genetic analysis, and 11 had the same mutation as the index case. All the mutation positive members had MEN1, while none of mutation-negative subjects had any sign of MEN1 syndrome. The frequencies of PHPT, pNET, and pituitary tumors in this kindred were 94.1% (16/17), 29.4% (5/17), and 29.4% (5/17) respectively. Conclusion: We report a rare MEN1 gene mutation which has been descibed in a single sporadic patient earlier. It was inherited by at least three generations of a large family, proving the strong dominant effect of the MEN1 phenotype. Further research may be conducted to clarify potential candidacy of this mutation as a hotspot for MEN1 patients, especially in the Turkish population
Challenges in the treatment of fibrodysplasia ossificans progressiva
No full textFibrodysplasia ossificans progressiva (FOP), is a rare autosomal dominant connective tissue disease with a prevalence of 1 in 2 million. It is characterized by congenital foot deformities and multiple heterotopic ossifications in fibrous tissue. It usually starts with painful soft tissue swellings occurring with attacks at the ages of three or four. The attacks develop spontaneously or after minor trauma, and gradually turn into heterotopic ossifications that cause joint limitations, growth defects, skeletal deformities and chronic pain. The average life expectancy is forthy, and most of the patients are lost due to pulmonary complications. FOP is often misdiagnosed as fibromatosis, desmoid tumour or cancer, bunion, myositis, arthritis and rheumatic diseases. After clinical suspicion, confirmatory genetic analysis should be used for the diagnosis. The treatment of FOP is currently supportive. An effective, proven method has not yet been established. Herein, we present an 18-year-old female patient with FOP who underwent different treatment modalities in a 5-year period. This case-based review reveals all available treatment approaches with at least 6-month follow-up for FOP in the literature
Determination of CYP2C19 Polymorphism, Side Effects, and Medication Adherence in Patients Who have Utilized Selective Serotonin Reuptake Inhibitors
No full textObjective: The aim of this study is to determine relationship of cytochrome P-450 2C19 (CYP2C19) enzymes polymorphism, side effects, and medication adherence in patients who have been diagnosed with major depression and have utilized selective serotonin reuptake inhibitors. Methods: Fifty-three major depression patients (mean of age: 33.25 +/- 11.29 years old; male/female: 7/46) were included in this study. Polymorphisms were determined from genomic DNA by using the 'Real-Time Polymerase Chain Reaction' method. Side effects and medication adherence levels were assessed by using the 'Toronto Side Effects Scale' and the four items medication adherence scale (Morisky, Green and Levine), respectively. Results: The most common side effects that patients reported were drowsiness/daytime somnolence (54.7%), malaise or fatigue (43.4%), sweating (43.4%), nausea (41.5%) and dry mouth (41.5%). Only nine (17%) patients were found to be highly adherent to their medication. When evaluating the CYP2C19 polymorphisms of patients, 37.7%, 24.5% and 20.8% of the patients were classified as intermediate, extensive and ultra-rapid metabolizers, respectively. Allele frequencies of CYP2C19*17 and CYP2C19* 2 was calculated as 24.5% and 27.4%, respectively. Although there were some differences in side effect scores and medication adherences among the polymorphism groups, these relationships were not found to be statistically significant. Conclusion: This study shows that patients who utilized antidepressants frequently experienced side effects and had low medication adherence. Another interesting finding is the high rate of ultrarapid metabolizers of CYP2C19
Novel mutations and deletions in cystic fibrosis in a tertiary cystic fibrosis center in Istanbul
No full textBackgroundCystic fibrosis (CF) genotyping has garnered increased attention since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 led to the identification of over 1700 mutations on chromosome 7. Yet, little is known about the genetic profile of CF patients in Turkey. This study sought to determine the mutation distribution among CF patients seeking care at Marmara University. MethodsTwo hundred fifty previously diagnosed CF patients were included in the study. CFTR gene exons 1 to 27 were amplified by a polymerase chain reaction and whole DNA sequencing was performed. Duplications and deletions were investigated by the multiplex ligation-dependent probe amplification (MLPA) technique in patients with one or two unidentified mutations in sequence analysis. ResultsCFTR mutation analysis revealed 80 mutations and five large deletions were present in our study population. The five most common mutations were (delta) F508 (c.1521-1523delCTT) (28.4%), 1677delTA (c.1545-1546delTA) (6.4%), 2789+5G->A (c.2657+5G>A) (5.8%), N1303K (c.3909C>G) (2.4%), and c.2183AA->G (c.2051-2052delAAinsG) (4.0%). Large deletions were found in 16 patients. Four novel mutations and two novel deletions were detected in this study. ConclusionsWe have identified four novel mutations and two novel deletions using next-generation DNA sequencing and the MLPA technique and obtained an overall mutation detection rate of 91.4%. Detection of novel variants in CF patients will assist in genetic counseling and in determining appropriate patients for new therapies
Biallelic Mutations in DNAJB11are Associated with Prenatal Polycystic Kidney Disease in a Turkish Family
No full textPolycystic kidney disease (PKD) is a life-threatening condition resulting in end-stage renal disease. Two major forms of PKD are defined according to the inheritance pattern. Autosomal dominant PKD (ADPKD) is characterized by renal cysts, where nearly half of the patients suffers from renal failure in the 7th decade of life. Autosomal recessive PKD (ARPKD) is a rarer and more severe form presenting in childhood. Whole-exome sequencing (WES) analyses was performed to investigate molecular causes of the disease in the fetus. In this study, we present 2 fetuses prenatally diagnosed with PKD in a consanguineous family. WES analysis of the second fetus revealed a homozygous variant (c.740+1G>A) in DNAJB11 which is related to ADPKD. This study reveals that DNAJB11 biallelic mutations may cause an antenatal severe form of ARPKD and contributes to understanding the DNAJB11-related ADPKD phenotype. The possibility of ARPKD due to biallelic mutations in ADPKD genes should be considered in genetic counseling
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