The efficacy of tissue factor −603A/G and +5466A>G polimorphisms at the development of venous thromboembolism in cancer patients

Background and Aim: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. Although factor V Leiden (FVL) is the most common genetic defect causing thrombosis, the impact of gene abnormalities on thrombotic tendency in cancer patients remains poorly explored. Tissue factor (TF) is a major physiologic initiator of blood coagulation. This is the first study regarding the association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy. Materials and Me thods: The study consists of two groups: cancer patients with VTE were included as Group 1 (n = 46); Group 2 comprises 196 cancer patients without VTE. Restriction fragment length polymorphism method was used for the detection of polymorphisms of TF −603A/G in the 5՛upstream region and TF 5466A/G in intron 2. FVL, PT G20210A and MTHFR C677T polymorphisms were determined by using commercially available Light Cycler kits. The genotype and allele frequencies between the groups were compared using χ² or Fisher exact test, if appropriate. Results: No differences were observed in the distribution of TF gene −603A/G genotype frequencies between the groups. Although a slightly increased incidence of +5466GA genotype was in Group 1 (17.4% vs 11.2%), it did not achieve statistical significance. The prevalence of FVL was significantly greater in Group 1 compared with Group 2 (41.3% vs 4.1%, p 0.05). Conclusions: The present study did not show significant association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy, however, further larger studies including different ethnic population are needed to confirm our findings.Background and Aim: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. Although factor V Leiden (FVL) is the most common genetic defect causing thrombosis, the impact of gene abnormalities on thrombotic tendency in cancer patients remains poorly explored. Tissue factor (TF) is a major physiologic initiator of blood coagulation. This is the first study regarding the association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy. Materials and Me thods: The study consists of two groups: cancer patients with VTE were included as Group 1 (n = 46); Group 2 comprises 196 cancer patients without VTE. Restriction fragment length polymorphism method was used for the detection of polymorphisms of TF −603A/G in the 5՛upstream region and TF 5466A/G in intron 2. FVL, PT G20210A and MTHFR C677T polymorphisms were determined by using commercially available Light Cycler kits. The genotype and allele frequencies between the groups were compared using χ² or Fisher exact test, if appropriate. Results: No differences were observed in the distribution of TF gene −603A/G genotype frequencies between the groups. Although a slightly increased incidence of +5466GA genotype was in Group 1 (17.4% vs 11.2%), it did not achieve statistical significance. The prevalence of FVL was significantly greater in Group 1 compared with Group 2 (41.3% vs 4.1%, p 0.05). Conclusions: The present study did not show significant association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy, however, further larger studies including different ethnic population are needed to confirm our findings

47,XYY Sendromlu Bir Olgu

Erkeklerde ilave Y kromozom varlığı, nispeten yaygın olarak meydana gelmektedir. 1000 canlı erkek doğumda bir görülmektedir. Bir disjunction hatası, ya paternal mayoz II esnasında veya postzigotik mitotik hata sonucu meydana gelmektedir. Bu her iki durum diğer kromozomlarda nadir olarak görülmektedir. Cinsiyet kromozom anormalliklerinin psikozlarla ilişkisi olduğu bilinmektedir. 47,XYY erkeklerde fazla sayıda olan Y kromozom genleri, normal erkeklere göre daha büyük kraniofasiyel boyutlara neden olabilir. XYY bileşiminin üzerinde son yıllarda çok durulmuştur. XYY kromozomları olan bireyler erkeksi bir dış görünüm taşırlar. Uzun boylu olurlar ve normal bir zekaya sahiptirler. Fakat bu kimselerin anormal kromozom bileşimleriyle davranış biçimleri arasındaki bağlantı tam olarak çözümlenebilmiş değildir. Bu olgunun sunumunda, erken yaşta saptanarak, hasta ve yakınlarında oluşabilecek sosyo-psikolojik sorunlara çözüm bulunması ve hekimlere bu konuda yol gösterici olunması amaçlanmıştır. Klasik sitogenetik analiz sonucunda olgunun karyotipi 47,XYY olarak saptandı. Mozaiklik durumunu dışlayabilmek için fazla sayıda metafaz incelemesi yanı sıra, interfaz FISH tekniğiyle de inceleme yapılarak ekstra Y kromozom varlığı tespit edildi. Y kromozom varlığının kesin olarak ortaya konması için psödootozomal bölgeye (PAR) spesifik primerler kullanılarak cinsiyet tayini yapıldı. DNA izolasyonu periferik kandan elde edilen lenfositlerden gerçekleştirildi. Bu sendromlu olgularda, genetik danışmanlık sürecini de kapsayan, uygun sosyo-psikolojik yaklaşımda izlenecek yollar, klinik takip ve tanı süreci literatür bilgilerine dayalı olarak tartışılmıştır

Androjen Duyarsızlığı Sendromlu Bir Olgu

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THE EFFICACY OF TISSUE FACTOR −603A/G AND +5466A>G POLIMORPHISMS AT THE DEVELOPMENT OF VENOUS THROMBOEMBOLISM IN CANCER PATIENTS

Background and Aim: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. Although factor V Leiden (FVL) is the most common genetic defect causing thrombosis, the impact of gene abnormalities on thrombotic tendency in cancer patients remains poorly explored. Tissue factor (TF) is a major physiologic initiator of blood coagulation. This is the first study regarding the association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy. Materials and Me thods: The study consists of two groups: cancer patients with VTE were included as Group 1 (n = 46); Group 2 comprises 196 cancer patients without VTE. Restriction fragment length polymorphism method was used for the detection of polymorphisms of TF −603A/G in the 5՛upstream region and TF 5466A/G in intron 2. FVL, PT G20210A and MTHFR C677T polymorphisms were determined by using commercially available Light Cycler kits. The genotype and allele frequencies between the groups were compared using χ² or Fisher exact test, if appropriate. Results: No differences were observed in the distribution of TF gene −603A/G genotype frequencies between the groups. Although a slightly increased incidence of +5466GA genotype was in Group 1 (17.4% vs 11.2%), it did not achieve statistical significance. The prevalence of FVL was significantly greater in Group 1 compared with Group 2 (41.3% vs 4.1%, p 0.05). Conclusions: The present study did not show significant association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy, however, further larger studies including different ethnic population are needed to confirm our findings.Background and Aim: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. Although factor V Leiden (FVL) is the most common genetic defect causing thrombosis, the impact of gene abnormalities on thrombotic tendency in cancer patients remains poorly explored. Tissue factor (TF) is a major physiologic initiator of blood coagulation. This is the first study regarding the association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy. Materials and Me thods: The study consists of two groups: cancer patients with VTE were included as Group 1 (n = 46); Group 2 comprises 196 cancer patients without VTE. Restriction fragment length polymorphism method was used for the detection of polymorphisms of TF −603A/G in the 5՛upstream region and TF 5466A/G in intron 2. FVL, PT G20210A and MTHFR C677T polymorphisms were determined by using commercially available Light Cycler kits. The genotype and allele frequencies between the groups were compared using χ² or Fisher exact test, if appropriate. Results: No differences were observed in the distribution of TF gene −603A/G genotype frequencies between the groups. Although a slightly increased incidence of +5466GA genotype was in Group 1 (17.4% vs 11.2%), it did not achieve statistical significance. The prevalence of FVL was significantly greater in Group 1 compared with Group 2 (41.3% vs 4.1%, p 0.05). Conclusions: The present study did not show significant association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy, however, further larger studies including different ethnic population are needed to confirm our findings

Fırat Üniversitesi Tıp Fakültesi Tıbbi Biyoloji ve Genetik Anabilim Dalında 2000-2005 Yılları Arasında Saptanan Down Sendromlu Olguların Periferik Kan Sitogenetik Analiz Sonuçları ve Klinik Değerlendirmeleri

Trizomiler gametogenez sırasında oluşan "meiotic nondisjunction" sonucu meydana gelir. İnsanlarda en sık görülen ve en iyi bilinen trizomi grubu, trizomi 21 veya Down sendromudur. Trizomi 21, insanlardaki mental retardasyon ve karakteristik fiziksel bulgulara eşlik eden en yaygın kromozom anormalliklerinden biridir. Bu çalışmamızda, 2000-2005 yılları arasında merkezimizde sonuç verilen 167 Down sendromlu olgunun klinik ve sitogenetik analizleri retrospektif olarak değerlendirilmiştir. Olgular, çeşitli merkezlerden klinik özellikleri sebebiyle genetik tanı için laboratuvarımıza gönderilmiş olup periferik kandan kromozom analizi yapılmıştır. Toplam 167 olgunun 91’i erkek (%54.4), 76’sı kız (%45.5) çocuğudur. Olguların 162’si (%97) klasik tip Down sendromu gösterirken, 2 olgu (%1.1) mozaik, 3 olgu (%1.7) translokasyon tipi Down sendromudur. Translokasyon tipi 1 olguda t(21;21), 2 olguda t(14;21) şeklindedir. Sitogenetik analiz sonuçları literatürde bildirilen oranlarla uyumludur. Ortalama anne yaşı 34.04’dür. Bu çalışmada ayrıca Down sendromlu olguların klinik özellikleri de değerlendirilmiştir. Olguların hemen hemen hepsine merkezimizde genetik danışmanlık verilmiştir. Klinik tanının kesinleşmesiyle birlikte, aileye uygun bir biçimde danışmanlık verilmelidir

Fırat Üniversitesi Tıp Fakültesi Tıbbi Biyoloji ve Genetik Anabilim Dalı’nın 2000-2005 Yılları Arasındaki Amniyosentez ve Kordosentez Sonuçları

Bu çalışmamızda, 2000-2005 yılları arasında merkezimizde sonuç verilen, 502 amniyotik sıvı ve 48 kord kanı örneğinde yapılan fetal kromozom analizleri, retrospektif olarak değerlendirilmiştir. 502 amniyosentez olgusunun 23’ünde (%4.58) kromozomal anomali saptanmıştır. Bu anomalilerden altısı trizomi-21, ikisi trizomi-13 ve ikisi trizomi-18 olmak üzere toplam 10 (%1.99)’u sayısaldır. Yedi vakada heterokromatik bölge artışı, üç vakada, inversiyon ve üç vakada translokasyon olmak üzere toplam 13 (%2.58) vakada yapısal anomali tespit edilmiştir. 48 kordosentez olgusunda trizomi-13, 18 ve 21 açısından, 3 vakada sayısal anomali tespit edilmiştir. Amniyosentez ve kordosentez endikasyonları; ileri anne yaşı, üçlü testte yüksek risk, ileri anne yaşı ile beraberlik gösteren üçlü testte yüksek risk, ultrasonda anomali bulgusu, Down Sendromlu ve anomalili bebek öyküsü olarak sınıflandırılmıştır. Anomali saptanan olgulara merkezimizde genetik danışmanlık verilmiştir

Neuromuscular disease genetics in under-represented populations: increasing data diversity

Neuromuscular diseases (NMDs) affect similar to 15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management.We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions.We recruited 6001 participants in the first 43 months. Initial genetic analyses 'solved' or 'possibly solved' similar to 56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a similar to 59% 'solved' and similar to 13% 'possibly solved' outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research.In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally.Wilson et al. present the findings of an international partnership established to study genetic causes of neuromuscular diseases in under-represented diverse populations from 12 low-middle income sites. A genetic cause was identified in similar to 55% of cases and similar to 30% of variants were novel, improving understanding of neuromuscular disease genetics.Functional Genomics of Muscle, Nerve and Brain Disorder