Sonay Temurhan

Relationship between clinical findings and genetic mutations in patients with familial Mediterranean fever

BackgroundFamilial Mediterranean fever (FMF) is one of the most frequent genetic diseases encountered in the Mediterranean region. We aimed to investigate the correlation between genetic mutations and the clinical findings in 562 patients with FMF.MethodsIn this retrospective cross-sectional study conducted with patients’ files between 2006, and 2013, reverse hybridization assay for MEFV gene mutations was used and the 12 most frequent mutations were screened. Mutation types and clinical findings were compared with variance analysis.ResultsThe mean age was 6.9u2009±u20093.4xa0years (range, 1.8-11.6xa0years). The most common symptom was fever (97.3xa0%). Thirty-four of the patients (6.04xa0%) were admitted with periodic fever only. Of these patients, M694V was the most common mutation type (73.5xa0%). The percentage of the patients predominantly presenting with recurrent abdominal pain was 77.78xa0% and the most frequent mutations were M694V and E148Q. The rate of arthritis and arthralgia was significantly higher in patients with M694V and E148Q mutations. Chest pain was reported more often in patients homozygous for M694V (61.4xa0%). Pericardial effusion was documented in the echocardiography of 10.9xa0% of the 229 children with chest pain. Some patients had both FMF and Henoch Schönlein purpura (HSP), and were more likely to harbor either homozygote M694V or E148Q mutations. The frequency of episodes was higher in patients with homozygous M694V mutations (number of attacksu2009=u20094.4u2009±u20091.6/month). Proteinuria was detected in 106 patients of cases (29.2xa0%), at an average of 854u2009±u2009145xa0mg/L. Most of the patients with proteinuria and elevated serum amyloid-A had homozygous M694V mutation.ConclusionThe most common mutation in children in Turkey with FMF is the M694V mutation. Recurrent abdominal pain, arthritis or arthralgia, chest pain, and pericarditis were commonly seen in patients with M694V and E148Q mutations.

Immunosuppressive Treatment in C3 Glomerulopathy: Is it Really Effective?

Background: C3 glomerulopathy (C3GP) is a recently identified and described disease that has a high risk of progressing into end-stage renal disease. We aimed to evaluate the effects of various immunosuppressive regimens on C3GP progression because there are conflicting data on the treatment modalities. Methods: In this retrospective study of 66 patients with C3GP, 27 patients received mycophenolate mofetil (MMF)-based treatment, 23 received non-MMF-based treatment (prednisolone or cyclophosphamide), and 16 received conservative care. The study groups were compared with each other with specific focus on primary outcomes defined as (1) kidney failure and (2) estimated glomerular filtration rate (eGFR) decline ≥50% from the baseline value. Results: Overall, 17 (25.8%) patients reached the primary outcome after a median period of 28 months. The number of patients who reached the primary outcome were similar among the study groups (MMF-based: 8/27 [29.6%], non-MMF-based: 4/23 [17.4%], and conservative care: 5/16 [31.3%], p = 0.520). In the Cox regression analysis, age (HR 0.912, p = 0.006), eGFR (HR 0.945, p = 0.001), and proteinuria levels (HR 1.418, p = 0.015) at the time of biopsy, percentage of crescentic (HR 1.035, p = 0.001) and sclerotic glomeruli (HR 1.041, p = 0.006), severity of interstitial fibrosis (HR 1.981, p = 0.048), as well as no remission of proteinuria (HR 2.418, p = 0.002) predicted the primary outcome. Conclusion: Although patients receiving immunosuppressive treatments had higher proteinuria and lower serum albumin at baseline, there were no differences between these patients and those receiving conservative care alone in proteinuria remission or in the decline of renal function. Younger age, higher proteinuria, lower eGFR, and the presence of crescentic and sclerotic glomeruli, severity of interstitial fibrosis, and no remission of proteinuria predicted the progression of kidney disease.

A Novel Biomarker for Post-Transplant Recurrent IgA Nephropathy

BACKGROUNDnThe serum levels of galactose-deficient immunoglobulin (Ig)A1 (Gd-IgA1) represent the most promising candidate biomarker for IgA nephropathy (IgAN). The aim of this study was to evaluate the serum levels of Gd-IgA1 as a novel noninvasive biomarker for post-transplant IgAN recurrence.nnnMETHODSnSerum Gd-IgA1 levels of 18 patients with recurrent IgAN were compared with control renal transplant recipients (nxa0= 23) with non-recurrent IgAN and control non-transplant IgAN patients (nxa0= 44) and healthy relatives (nxa0= 11). Serum Gd-IgA1 levels of patients were measured with the use of KM55 enzyme-linked immunosorbent assay (ELISA). The effects of serum Gd-IgA1 concentrations on IgAN recurrence, post-transplant events, and graft survival were evaluated.nnnRESULTSnAll recurrent IgAN patients presented with renal dysfunction (mean serum creatinine, 1.62 ± 0.39 mg/dL) and detectable proteinuria at the time of diagnosis. Serum Gd-IgA1 levels of recurrent IgAN patients (8735 ± 10854 ng/mL [log10: 3.71 ± 0.45]) were significantly higher than those of non-recurrent IgAN patients (4790 ± 6089 ng/μL [log10: 3.31 ± 0.64]) (Pxa0= .027). Serum Gd-IgA1 levels of non-transplant IgAN patients were significantly higher (8791 ± 8700 ng/μL [log10: 3.79 ± 0.36]) than those of non-recurrent IgAN patients (4790 ± 6089 ng/μL [log10: 3.31 ± 0.64]) and healthy relatives (2615 ± 1611 ng/μL [log10: 3.34 ± 0.27]) (Pxa0< .001 and Pxa0= .021, respectively). Receiver-operating characteristic curve analysis revealed that the area under the curve for recurrence of IgAN was 0.69 (0.53-0.85) for serum Gd-IgA1 (Pxa0= .038). Biopsy-confirmed allograft rejection rates were similar in the recurrent IgAN group [3 (17%)] compared with the non-recurrent IgAN [6 (26%)] group (Pxa0= .47). Graft failure rate was not also significantly different in the recurrent IgAN group [4 (22.2%)] compared with the non-recurrent IgAN group [2 (8.7%)] (Pxa0= .224).nnnCONCLUSIONSnThis novel lectin-independent Gd-IgA1 ELISA that can detect serum Gd-IgA1 in patients with recurrent IgAN can be used as a biomarker for diagnosis and activity assessment of post-transplant recurrent IgAN.

Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective.

Objective: Alpha thalassemia syndromes are caused by mutations on one or more of the four α-globin genes. Mutations could be either more commonly deletional or non-deletional. As some deletions (3.7 and 4.2) cause α+-thalassemia, some cause (-20.5, MED, THAI, FIL) α0 -thalassemia. The aim of this study was to determine alpha thalassemia mutations in patients with unsolved hypochromic microcytic anemia and to evaluate types of mutations. Material and Methods: Two hundred six patients with hypochromic microcytic anemia were evaluated for alpha thalassemia. A venous blood sample of 2 mL was drawn from each patient for DNA isolation. The samples were investigated for α-thalassemia mutations by using the Vienna Lab α-Globlin StripAssay TM commercial kit. Results: Fourteen different mutations were determined in 95 (46.1%) patients. The most common mutation was the 3.7 single gene deletion and was found in 37 patients (n=37/95, 39%). Others common mutations were the 20.5 kb double gene deletion (n=20 patients, 21%), MED double gene deletion (n=17 patients, 17.9%), α2 IVS1 (n=10 patients, 10.5%), α2 cd142 Hb Koya Dora (n=6 patients, 6.3%), α2 polyA1 (Saudi type) (n=6 patients, 6.3%), 4.2 single gene deletion (n=4 patients, 4.2%), α1 cd14 (n=2 patients, 2.1%), and -FIL mutation (n=2 patients 2.1%), respectively. Hb Adana, Hb Icaria, α2 init cd and α2 polyA2 (Turkish type) were found in 1% of the patients (n=1). Seven patients (7.4%) had α-thalassemia triplication. In our study, three mutations (Hb Icaria, α1 cd14, α2 init.cd) were determined firstly in Turkey. Seven mutations (-SEA, -THAI, Hb Constant Spring, α2 cd19, α2 cd59, α2 cd125, Hb Paksé) were not determined in this study. Conclusion: Alpha thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemia especially in cases without iron deficiency and b-thalassemia carrier state. Genetic testing should be performed for the suspicious cases. We also recommend that a national database with all mutations in Turkey should be created to screen the alpha thalassemia cost-effectively.

The Effect of TGFB1 and CD14 Gene Polymorphisms on the Clinical Findings of Cystic Fibrosis in Turkish Patients

Abstract Significant effects of several modifying genes on the clinical features of cystic fibrosis (CF) have been reported. In the present study, the researchers investigated the effects of transforming growth factor beta 1 (TGFB1) and cluster of differentiation 14 (CD14) polymorphisms on the clinical status of patients with CF. The present study included sixty-five patients with CF and eighty five healthy controls with no pulmonary disease. Single-nucleotide polymorphisms in the TGFB1 gene (rs1800469, rs1800470, rs8179181) were studied using DNA sequence analyses; the CD14 gene polymorphism rs2569190 was evaluated using restriction fragment length polymorphism analysis. The frequency of rs1800469 (TT genotype) was significantly higher in the healthy controls than in the patients with CF. Thus, the TT genotype may be protective against CF. Although rs8179181 (CT genotype) may have an overall negative effect, this genotype may have a favourable effect on growth parameters. However, these results should be confirmed in larger studies.