Co-circulation of West Nile virus and distinct insect-specific flaviviruses in Turkey

Background: Active vector surveillance provides an efficient tool for monitoring the presence or spread of emerging or re-emerging vector-borne viruses. This study was undertaken to investigate the circulation of flaviviruses. Mosquitoes were collected from 58 locations in 10 provinces across the Aegean, Thrace and Mediterranean Anatolian regions of Turkey in 2014 and 2015. Following morphological identification, mosquitoes were pooled and screened by nested and real-time PCR assays. Detected viruses were further characterised by sequencing. Positive pools were inoculated onto cell lines for virus isolation. Next generation sequencing was employed for genomic characterisation of the isolates. Results: A total of 12,711 mosquito specimens representing 15 species were screened in 594 pools. Eleven pools (2%) were reactive in the virus screening assays. Sequencing revealed West Nile virus (WNV) in one Culex pipiens (s.l.) pool from Thrace. WNV sequence corresponded to lineage one clade 1a but clustered distinctly from the Turkish prototype isolate. In 10 pools, insect-specific flaviviruses were characterised as Culex theileri flavivirus in 5 pools of Culex theileri and one pool of Cx. pipiens (s.l.), Ochlerotatus caspius flavivirus in two pools of Aedes (Ochlerotatus) caspius, Flavivirus AV-2011 in one pool of Culiseta annulata, and an undetermined flavivirus in one pool of Uranotaenia unguiculata from the Aegean and Thrace regions. DNA forms or integration of the detected insect-specific flaviviruses were not observed. A virus strain, tentatively named as “Ochlerotatus caspius flavivirus Turkey”, was isolated from an Ae. caspius pool in C6/36 cells. The viral genome comprised 10,370 nucleotides with a putative polyprotein of 3,385 amino acids that follows the canonical flavivirus polyprotein organisation. Sequence comparisons and phylogenetic analyses revealed the close relationship of this strain with Ochlerotatus caspius flavivirus from Portugal and Hanko virus from Finland. Several conserved structural and amino acid motifs were identified. Conclusions: We identified WNV and several distinct insect-specific flaviviruses during an extensive biosurveillance study of mosquitoes in various regions of Turkey in 2014 and 2015. Ongoing circulation of WNV is revealed, with an unprecedented genetic diversity. A probable replicating form of an insect flavivirus identified only in DNA form was detected

Duplication analysis in Turkish Charcot-Marie tooth Type 1A patients using short tandem repeat markers

11th International Congress on Neuromuscular Diseases -- JUL 02-07, 2006 -- Istanbul, TURKEYWOS: 000239229400314

Spinal Muscular Atrophy and Its Molecular Genetics

Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases, affecting aproximately 1 in 6,000 - 10,000 live births, and with a carrier frequency of aproximately 1 in 40- 60. The childhood SMAs can be classified clinically into three groups. Type I (Werdnig-Hoffmann) is the most severe form, with onset at ‹ 6 months of age and with death typically at ‹2 years of age. Type II SMA patients display an intermediate severity, with onset at ‹18 months of age and with an inability to walk. Type III (Kugelberg –Walender) individuals are able to walk independently and have a relatively mild phenotype, with onset at ›18 months of age. The gene involved in type I–III SMA has been mapped to 5q12-q13 by linkage analysis, and refined to a region of about 500 kb. The region contains a large inverted duplication consisting of at least four genes, which are present in a telomeric (t) and a centromeric (c) copy: survival motor neuron gene (SMN1 or SMNt and SMN2 or SMNc); neuronal apoptosis inhibitory protein gene (NAIP); basal transcription factor subunit p44 (BTFp44t and BTFp44c); and a novel protein with unknown function H4F5. Although homozygous deletions encompassing all these genes are found in SMA patients, it is now well established that mutations or deletions of SMN1 (MIM#600354) cause the disease. SMN2 (MIM# 601627) gene, however, does not prevent the disease but attenuates disease severity. Therefore, upregulating functional SMN protein level via inducing gene expression and/or restoring splicing is an important therapeutic approach such as use of histone deacetylase (HDAC) inhibitors. [Archives Medical Review Journal 2012; 21(1.000): 1-26

Mutation analysis of 6 spinocerebellar ataxia (SCA) types in patients from southern Turkey

Background/aim: Spinocerebellar ataxias (SCAs) are complex clinical and genetically heterogeneous, mostly autosomal dominant neurodegenerative diseases. At present, more than 30 hereditary SCA types have been associated with different gene mutations. In this study, the frequency distribution of the 6 SCA types 1, 2, 3, 6, 7, and 17 in the Turkish population was investigated with respect to clinical features. Materials and methods: 159 patients who received a diagnosis of SCA and 42 healthy controls from Adana, Mersin, Gaziantep, Hatay, and Osmaniye provinces were included in the study. DNA samples were isolated from 2 mL blood samples and the number of trinucleotide repeats (TNRs) for each SCA type was detected using PCR-RFLP technique and sequencing. Results: Of the 6 SCA types that were studied, 4 types, SCA 1, 3, 7, and 17, were positive and all heterozygous for expansions. SCA types 1 and 17 had higher frequencies, 4.4% and 3.8%, respectively, than SCA types 3 and 7. The clinical data of patients were also evaluated to correlate with the increased TNR numbers. Conclusion: This study, being the first mutation record of SCAs in this area, indicated that 9.4% of cases belonged to 4 types, SCA 1, 3, 7, and 17.Background/aim: Spinocerebellar ataxias (SCAs) are complex clinical and genetically heterogeneous, mostly autosomal dominant neurodegenerative diseases. At present, more than 30 hereditary SCA types have been associated with different gene mutations. In this study, the frequency distribution of the 6 SCA types 1, 2, 3, 6, 7, and 17 in the Turkish population was investigated with respect to clinical features. Materials and methods: 159 patients who received a diagnosis of SCA and 42 healthy controls from Adana, Mersin, Gaziantep, Hatay, and Osmaniye provinces were included in the study. DNA samples were isolated from 2 mL blood samples and the number of trinucleotide repeats (TNRs) for each SCA type was detected using PCR-RFLP technique and sequencing. Results: Of the 6 SCA types that were studied, 4 types, SCA 1, 3, 7, and 17, were positive and all heterozygous for expansions. SCA types 1 and 17 had higher frequencies, 4.4% and 3.8%, respectively, than SCA types 3 and 7. The clinical data of patients were also evaluated to correlate with the increased TNR numbers. Conclusion: This study, being the first mutation record of SCAs in this area, indicated that 9.4% of cases belonged to 4 types, SCA 1, 3, 7, and 17

Determination of Genotypic and Phenotypic Characteristics of Friedreich’s Ataxia and Autosomal Dominant Spinocerebellar Ataxia Types 1, 2, 3, and 6

Amaç: Bu çalışmada klinik, elektrofizyolojik bulgular ışığında herediter ataksi olarak değerlendirilen olguların moleküler genetik incelemeleri de dikkate alınarak Freidreich Ataksisi (FA) ve otozomal dominant Spino Serebellar Ataksi (SCA) 1, 2, 3 ve 6 açısından genotipik ve fenotipik yönden irdelenmesi amaçlanmıştır. Yöntem: Çalışmaya Nöroloji kliniğine başvuran, klinik, laboratuar ve elektrofizyolojik bulgular eşliğinde herediter serebellar ataksi olarak tanınan 129 indeks olgu yanı sıra aile taraması sonucu 15 kardeş hasta (toplam144 olgu) alınmış ve genetik analizleri yapılmıştır. Olguların ayrıntılı fizik ve nörolojik muayene, pedigri analizi, elektronörografi, uyarılmış potansiyel çalışmaları, serebral-spinal manyetik rezonans görüntüleme (MR) ve ekokardiyografik incelemeleri yapılmıştır. Hastalardan kan örneği alınarak Freidreich ataksisi yanı sıra SCA 1, 2, 3 ve 6 açısından moleküler genetik çalışmalar yapılmış, verilerin istatistiksel analizinde SPSS (Statistical Package for the Social Sciences Inc; Chicago, IL, ABD) 17,0 paket programı kullanılmıştır. Bulgular: Olguların %50'ye yakını Freidreich ataksisi olarak tanınırken iki olgu SCA 1, iki olgu ise SCA 6 olarak tanınmıştır. Sonuç: Serimizde herediter zeminde gelişen serebellar ataksili olguların %47,2'sini FA'lı hastalar oluşturmuş olup otozomal dominant kalıtılan spinoserebellar ataksilerden SCA1 ve SCA6 birer ailede saptanmıştır. Bu veriler herediter zeminde geliştiğini düşündüğümüz serebellar ataksili bir hasta ile karşı karşıya kaldığımızda olgunun öncelikli olarak FA yönünden değerlendirmemiz gerektiğini göstermektedir.Introduction: This study aimed to analyze the genotypic characteristics of Friedreich’s ataxia (FA) and autosomal dominant ataxias [such as spinocerebellar ataxia (SCA) types 1, 2, 3, and 6] using molecular and biological methods in hereditary cerebellar ataxia considering both clinical and electrophysiological findings. Methods: The study included 129 indexed cases, who applied to the neurology department and were diagnosed with hereditary cerebellar ataxia through clinical, laboratory, and electrophysiological findings, and 15 sibling patients who were diagnosed through family scanning (144 cases in total); their genetic analyses were also performed. Detailed physical and neurological examinations, pedigree analyses, electroneurography, evoked potentials, cerebral–spinal magnetic resonance imaging, and echocardiographic analyses were performed for all cases. Blood samples were collected from patients, and the genotypic characteristics of autosomal dominant SCA types 1, 2, 3, and 6 were investigated. Statistical analyses were performed with the Statistical Package for the Social Sciences (SPSS Inc; Chicago, IL, USA) 17.0. Results: Almost 50% of patients were defined as FA. Moreover, two SCA1 cases and one SCA6 case were detected. Conclusion: In our study, 47.2% of patients with FA had developed hereditary cerebellar ataxia. Ground and autosomal dominant-linked SCA1 and SCA6 were each detected in one family. These data suggest that patients with cerebellar ataxia of hereditary origin should be primarily examined for FA