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© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease.

Recombinant chromosome 4 is a very rare chromosomal aberration with eleven cases reported in the literature up to date. Here we report a five years old male patient with de novo rec(4) dup(4p) del(4q). The physical examination findings were as follows: caput quadratum, flat occiput, low frontal hairline, hypertelorism, ptosis, blepharophimosis, high arched eyebrows, flat nasal root with antevert nostrils and short nose, long and smooth philtrum, thin upper lip with triangular mouth, high arched palate, dental anomalies, large low-set ears, short neck, broad chest with widely spaced nipples, micropenis, cryptorchidism. Conventional cytogenetic analysis revealed the karyotype as 46,XY,rec(4)dup(4p14p16.3)del(4q34.3q35). Flourescence in-situ hybridization (FISH) analysis with sub-telomeric probes for 4p and 4q showed duplication of 4p and deletion of 4q in recombinant chromosome 4. His parents’ chromosomal analysis and sub-telomeric FISH analysis were both normal. The patient’s final karyotype was reported as 46,XY,rec(4)dup(4p16.3p14)del(4q34.4q35).arr[hg19]4p16.3p14(68,345-36,018)x3,4q34.3q35(177,676,319-190,957,460)x1 detected by Microarray. According the literature all cases with recombinant chromosome 4 have similar clinical findings. Except for our case only one case in the literature has been reported to be de novo. In conclusion, we reported a very rare case of recombinant chromosome 4, which has the largest deletion and duplication in the literature. Further cases with similar findings would help delineation of the symptoms related to the aberration., Rekombinant kromozom 4, nadir görülen yapısal birkromozomal anomalidir. Literatürde bugüne kadar on bir vaka bildirilmiştir. Buyazıda 5 yaşında de novorec(4)dup(4p)del(4q) karyotipine sahip bir erkek hasta bildirilmiştir. Hastanınfizik muayene bulguları; kaput kuadratum, yassı oksiput, düşük frontal saççizgisi, hipertelorizm, pitozis, blefarofimozis, yüksek kemerli kaşlar,antevert burun delikleri ile düz burun kökü, kısa burun, uzun ve pürüzsüzfiltrum, üçgen ince üst dudak, yüksek damak, diş anomalileri, geniş, düşükkulaklı kulaklar, kısa boyun, ayrık meme uçları, mikropenis, kriptorşidizmşeklinde sıralanmaktadır. Konvansiyonel sitogenetik analiz sonucunda 46,XY,rec(4)dup(4p14p16.3)del(4q34.3q35)karyotipi saptanmıştır. 4p ve 4q kromozomal bölgelerine spesifik subtelomerikproblarla yapılan floresan in-situ hibridizasyon (FISH) analizi sonucundarekombinant kromozom 4'te, 4p duplikasyonu ve 4q delesyonu saptanmıştır.Hastanın son karyotipi 46,XY,rec(4)dup (4p16.3p14)del(4q34.4q35).arr[hg19]4p16.3p14 (68.345-36.018) x3,4q34.3q35 (177,676,319-190,957,460) olarak raporedilmiştir. Literatürde bildirilen tüm rekombinant kromozom 4 olguları benzerklinik bulgulara sahiptir. Bizim olgumuz dışında literatürde sadece bir olgununde novo olduğu bildirilmiştir. Sonuçolarak, bu yazıda literatürdeki en büyük delesyon ve duplikasyona sahip nadirbir rekombinant kromozom 4 olgusu bildirilmştir.

AIM:To assess the association between age-related macular degeneration (AMD) and three single nucleotide polymorphisms (SNPs) related to the vascular endothelial growth factor (VEGF) gene.METHODS: The patients who were diagnosed with AMD were included in this prospective study. Three SNPs (rs1413711, rs2146323, and rs3025033) of the VEGF gene were genotyped by real-time polymerase chain reaction in the genomic DNA isolated from peripheral blood samples of the 82 patients and 80 controls.RESULTS: The genotype frequencies of rs1413711 and rs2146323 were not significantly different between the study group and the control group (P=0.072 and P=0.058). However, there was a significant difference in the genotype frequencies of these SNPs between the wet type AMD and dry type AMD (P=0.005 and P=0.010, respectively). One of the SNPs (rs1413711) was also found to be associated with the severity of AMD (P=0.001) with significant genotype distribution between early, intermediate, and advanced stages of the disease. The ancestral alleles were protective for both SNPs while the polymorphic alleles increased the risk for dry AMD.CONCLUSION: VEGF SNPs rs1413711 and rs2146323 polymorphisms are significantly associated with AMD subtypes in our population.

Yaşa bağlı makula dejenerasyonu (YBMD) hem genetik hem de çevresel risk faktörlerine sahip olan kompleks bir hastalıktır. Epigenetik faktörler de YBMD patogenezinde rol oynamaktadır. Mevcut genetik bilgi, geliştirilmiş risk değerlendirmesi ve genetik varyantların teşhisi için olanak sağlamaktadır. YBMD ile ilişkili en çok çalışılan genler, kompleman faktörü H (CFH) ve yaşa bağlı makulopati duyarlılığı 2 (ARMS2) 'dir. YBMD'de genetiğin rolünün daha iyi anlaşılması, gelecekte kişiselleştirilmiş tedavinin yolunu açabilecektir

OBJECTIVE: We aimed to determine the hot spot mutational frequencies of Enhancer of Zeste homolog 2 (EZH2) and cluster of differentiation 79B (CD79B) genes in a cohort of mature B-cell non-Hodgkin's lymphomas. PATIENTS AND METHODS: DNA samples from formalin-fixed and paraffin embedded (FFPE) tissues from a total of 37 patients with mature B-cell non-Hodgkin lymphomas were included in the study. Molecular genetic analysis was performed by direct sequencing of the DNA samples. RESULTS: We analyzed formaldehyde fixed-paraffin embedded (FFPE) tumor tissue samples from 17 female and 20 male patients with a median age of 63.7 years at the time of diagnosis. None of the patients had previously reported hot spot mutations in EZH2 and CD79B, but previously unreported single nucleotide variations of CD79B were present in nine patients. rs779833118 was the most frequent variation (7/37 patients, 18.9%). A non-synonymous variation rs757407417, which could have a potentially damaging outcome, was detected in two patients. CONCLUSIONS: None of the patients had well-known hot spot mutations in EZH2 and CD79B. However, we detected novel CD79B variations in mature B-cell non-Hodgkin's lymphoma patients. © 2016, Verduci Editore. All rights reserved.

Bladder cancer is the one of the most common cancers worldwide and O6-Methylguanine DNA Methyltransferase (MGMT) promoter methylation might be contributing to clinicopathological features of the disease. We analyzed formalin-fixed, paraffin-embedded bladder tissue samples from 101 patients with urothelial carcinoma. All samples were analyzed by real-time methylation-specific PCR. MGMT promoter methylation was detected in 15 (14.9%) of the samples and was not significantly different between any of the groups, although the number of high grade tumors with MGMT promoter methylation was twice the number of low grade tumors. Methylation of MGMT in high grade tumors might play a role in aggressive proliferation of the tumor cells and a poor prognosis.

ÖzetSTBM/VANGL (Strabismus/VanGogh Like) Gen Ekspresyonunun HepatosellülerKanser Hücre Dizilerinde Hücre Davranışı Üzerine Olan EtkileriG. Ozan ÇETİNDokuz Eylül Üniversitesi, Tıp Fakültesi, Tıbbi Biyoloji ve Genetik AD, İzmirHepatosellüler kanser (HCC) dünyadaki en yaygın beşinci kanser türüdür vebilinen etkin bir tedavisi bulunmamaktadır.Wnt düzlemsel hücre polaritesi yolunda yer alan ve transmembran bir proteinolan Van Gogh like 1 (Vangl1) proteini gelişimsel süreçte embriyonik hücrelerinplanar hücre polaritesi kazanmalarını sağlar ve konverjant ekstansiyon hareketindensorumludur. Erişkinde, spesifik olarak testis ve ovaryumda, bunların dışında beyindeve prostatta eksprese olur.VANGL1 ekspresyonu, aralarında HCC'in de bulunduğu çeşitli insan kanserhücre dizilerinde gösterilmiştir. Araştırmamızda, VANGL1 geni siRNA yöntemiylebaskılanan HCC hücrelerinde, bu baskılanmanın yol açacağı hücre davranışdeğişikliklerinin incelenmesi hedeflendi.HCC hücre dizilerinde, VANGL1 ekspresyonunun varlığı, RT-PCR ve gerçekzamanlı PCR yöntemleriyle gösterildi. İnternet tabanlı bir yazılım kullanılarakVANGL1 genine spesifik siRNA hedef bölgesi belirlendi. Bu hedefe yönelik saç tokasıyapısındaki siRNA'yı transkribe edecek DNA dizisi tasarlandı. pSilencer 4.1 CMVNeo plazmidine siRNA kalıbı eklenip HepG2 hücreleri plazmidle transfekte edildi.VANGL1 geninin baskılandığı koloniler RT-PCR ile saptandı. Bu kolonilerden eldeedilen protein lizatları western blotlama ile değerlendirilerek gen ekspresyonununbaskılandığı doğrulandı. VANGL1 geni baskılanmış hücrelerin motilite ve invazyonözellikleri Boyden odacık deney sistemi ile proliferasyon analizleri ise akımsitometresi ile değerlendirildi.VANGL1 geni sessizleştirilen HCC hücrelerinin motilite özellikleri,baskılanmayan hücrelere göre belirgin değişiklik göstermezken, invazyonyeteneklerinin üç kat azaldığı gözlendi. Proliferasyon analizinde, VANGL1 genisessizleştirilmiş hücrelerle atasal hücre grubu arasında S fazındaki hücre oranıaçısından belirgin farklılık gözlenmemiştir.Sonuçta Vangl1 hücre motilitesinden çok hücre invazyonunu etkilemektedir.Bu etkinin mekanizmasını ortaya çıkartmak üzere ileri araştırmalar yapılmalıdır.Anahtar Kelimeler: Wnt, VANGL1, hepatosellüler kanser, motilite, invazyon,proliferasyon, SummaryThe effects of STBM/VANGL (Strabismus/Van Gogh like) gene expression on cellbehaviour in hepatocellular cancer cell linesG. Ozan ÇetinDokuz Eylül University, Faculty of medicine, Department of Medical biology andGenetics, İzmirHepatocellular cancer (HCC) is the fifth most common cancer type and has noeffective treatment so far.Van Gogh like 1( Vangl1) protein, which is a transmembrane protein takingplace on Wnt planar cell polarity pathway, is important for embryonic cells to gainplanar cell polarity during developmental process and is also responsible fromconvergent extension. In adults, it is expressed spesifically in testis and ovarium as wellas in brain and prostat.VANGL1 expression has been reported in several human cancer cell linesincluding HCC. Our aim in this study was to investigate the behavior of HCC cellwhose VANGL1 gene was suppressed by siRNA method.The existence of VANGL1 expression in HCC cell lines was shown by RT-PCRand real time PCR methods. Internet based software program was used to define thetarget siRNA area spesific for VANGL1 gene. DNA line which transcribes the hairpinsiRNA for this target was designed. SiRNA insert was added to pSilencer 4.1 CMV Neoplasmid, later which was used to transfect HepG2 cells. The colonies having suppressedVANGL1 gene were examined by RT-PCR method. Suppression of the gene expressionwas proven by using western-blot method in assessing protein lisates provided by thecolonies. Motility and invasion of the cells having suppressed VANGL1 were assessedby Boyden chamber assay while proliferation analysis was assessed by flow cytometry.There was no difference in the motility of the HCC cells having suppressedVANGL1 where as the invasion capacity was decreased by 3 times.??. In proliferationanalysis, there was no difference in S phase cell ratio between VANGL1 suppressedcells and parental cells.As a conclusion, VANGL1 gene has an effect on cell invasion rather than cellmotility. Further investigations are needed to understand the mechanism of this effect.Key Words: Wnt, VANGL1, hepatocellular cancer, motility, invasion,proliferation 118

Yaşa bağlı makula dejenerasyonu (YBMD), özellikle gelişmiş ülkelerdeki geri dönüşümsüz görme kaybının en önemli nedenidir. YBMD gelişimindeki en önemli risk faktörü ileri yaştır. CFH genindeki rs1061170 polimorfizminin YBMD gelişimi açısından bağımsız bir risk faktörü olduğu gösterilmiştir. Bununla birlikte bu polimorfizme sahip hastalarda hastalığın gelişmemesi sonucunda YBMD ile ilişkili farklı genlerin araştırıldığı çalışmalarda, birçok gende YBMD?ye karşı koruyuculuk yaratabilecek polimorfizmler saptanmakla birlikte, YBMD ile ilişkili olabilecek yeni genler de araştırılmaya devam edilmektedir. Bu olgu-kontrol çalışmamızda, YBMD?ye sahip 87 hasta ve sağlıklı 80 bireyde, CFH genindeki rs1061170 polimorfizmine ek olarak, SKIV2L ve MYRIP genlerindeki rs429608 ve rs2679798 ve HIF1A genindeki rs11549465 ve rs11549467 polimorfizmlerinin dağılımlarını dizi analizi yöntemiyle belirledik. CFH genindeki rs1061170 polimorfizmi açısından en az 1 adet C alleli taşımanın YBMD gelişimini yaştan bağımsız olarak arttırdığını bulduk (OR= 2.42; 95%CI 1.22-4.81). Ek olarak, aynı polimorfizmdeki atasal T allelinin de YBMD?ye karşı koruyucu etkiye sahip olduğu görüldü (OR=0.53; 95%CI 0.34-0.83). Diğer genlerdeki polimorfizmlerin dağılımları açısından ise hasta ve kontrol gruplarımız arasında istatistiksel bir fark saptanmamıştır. Bu çalışma sonucunda CFH geni rs1061170 polimorfizminin ülkemiz popülasyonu için de YBMD ile ilişkili olduğu belirlendi. Araştırma sonucunda diğer genlerde yer alan polimorfizmlerin YBMD ile ilşkisi gösterilememiştir ancak bu konuda daha geniş gruplarla yapılacak çalışmalara gereksinim vardır. Age-related macular degeneration (AMD) is, especially in developed countries, one of the most important reasons of irreversible vision loss in advanced age. The most important risk factor is an advanced age. It has been shown that rs1061170 polymorphism in CFH gene is also an independent risk factor for AMD. However, disease-free patients with this polymorphism necessitate the investigation of other possible candidate genes. Thus, several number of polymorphisms both the ones with protective effect and the ones with causative effect have been identified and still being investigated. In this case-control study, we determine the distributions of rs1061170 (CFH), rs429608 (SKIV2L), rs2679798 (MYRIP) and rs11549465 and rs11549467 (HIF1A) polymorphisms via sequencing in 87 AMD patients and 80 healthy subjects. We found that having at least one C allele for rs1061170 polymorphism increases AMD risk independent from age (OR= 2.42; 95%CI 1.22-4.81). Furthermore, the ancestral T allele for rs1061170 polymorphism has protective effect for AMD (OR=0.53; 95%CI 0.34-0.83). There is no statistically significant difference for distributions of the other studied gene polymorphisms between patients and healthy subjects. As a conclusion, it has been identified that rs1061170 polymorphism of CFH gene is also associated with AMD in our population. Although no associations were documented for other polymorphisms, large-scale studies should be designed to clearly identify these associations in our population. 90