Erratum: The genomic architecture of NLRP7 is Alu rich and predisposes to disease-associated large deletions

NLRP7 is a major gene responsible for recurrent hydatidiform moles. Here, we report 11 novel NLRP7 protein truncating variants, of which five deletions of more than 1-kb. We analyzed the transcriptional consequences of four variants. We demonstrate that one large homozygous deletion removes NLRP7 transcription start site and results in the complete absence of its transcripts in a patient in good health besides her reproductive problem. This observation strengthens existing data on the requirement of NLRP7 only for female reproduction. We show that two other variants affecting the splice acceptor of exon 6 lead to its in-frame skipping while another variant affecting the splice donor site of exon 9 leads to an in-frame insertion of 54 amino acids. Our characterization of the deletion breakpoints demonstrated that most of the breakpoints occurred within Alu repeats and the deletions were most likely mediated by microhomology events. Our data define a hotspot of Alu instability and deletions in intron 5 with six different breakpoints and rearrangements. Analysis of NLRP7 genomic sequences for repetitive elements demonstrated that Alu repeats represent 48% of its intronic sequences and these repeats seem to have been inserted into the common NLRP2/7 primate ancestor before its duplication into two genes

Genetik danışmanlık ve önemi

Genetic diseases occur due to abnormalities consisting in the genomic material of the living beings. It may transmit from one generation to the other but it may also be limited only in the affected individual. Everyone carries a risk for a particular genetic disease but a greater risk is observed in some families. Today, in parallel with the development in genetics, an increasing demand from the public and medical field is present. This situation brings importance of informing individuals, their families and their children of their present or future genetic conditions, a process called genetic counseling. Although there is no treatment for most of the genetic diseases, genetic counseling has an important role in conditions such as family planning, diagnosis of genetic diseases and possible novel treatment protocols. In our country, there are genetic centers based in the university hospitals, state hospitals and private medical centers. The importance of genetics and genetic counseling is gradually being understood by the people who have been referred for genetic counseling, and by the physicians and other health care workers who refer those providers to the genetic centers. They ensure more individuals receive this service as well. In this review, genetic counseling, its status in our country and in the world is presented widely with up-to-date literature.Genetik hastalıklar, canlıların genomik materyallerinde oluşan anormallikler nedeniyle meydana gelen hastalıklardır. Kuşaktan kuşağa aktarılabileceği gibi, sadece ortaya çıktığı bireyle de sınırlı kalabilir. Her insan belli bir genetik hastalık riski taşımakla birlikte bazı ailelerde bu risk daha fazla olarak gözlenmektedir. Günümüzde genetik biliminde sağlanan gelişmelere paralel olarak bu alana talep, hem toplumsal hem de tıp alanında gittikçe artış göstermektedir. Bu durum genetik danışmanlık olarak adlandırılan, bireylerin kendilerinde, ailelerinde, ileride doğacak çocuklarında mevcut veya ortaya çıkabilecek genetik hastalıklar hakkında her türlü bilgi verme işlemini çok önemli hale getirmektedir. Genetik danışmanlık, genetik hastalıkların tanınması ortaya çıkabilecek tedavi yöntemlerinin uygulanması, aile planlaması gibi durumlarda önemli bir yere sahiptir. Ülkemizde üniversite hastaneleri, devlet hastaneleri ve bazı özel merkezler dahilinde genetik tanı merkezleri bulunmaktadır. Genetik danışmanlık hizmeti almak üzere merkezlere başvuran bireyler, bu bireyleri yönlendiren doktorlar ve diğer sağlık hizmeti görevlileri gün geçtikçe genetik ve genetik danışmanlık sürecinin önemini anlamakta ve daha çok kişinin bu hizmeti almasını sağlamaktadırlar. Bu derlemede genetik danışmanlık konusu, ülkemiz ve dünyadaki durumu güncel literatür bilgileri ışığında sunulmaktadır

Pediatrik Cerrahide Sık Karşılaşılan Konjenital Anomalilere Genetik Yaklaşım

Genetic approach to common congenital anomalies in pediatric surgery Congenital anomalies which occur 3-4% of births are developmental defects and are important cause of perinatal mortality and morbidity. When considering these anomalies in the newborn period or later, first they should be classified and possible treatment options should be reviewed promptly. At this stage, Pediatric Surgery Departments serve and contribute to the correction of these abnormalities. On the other hand, genetic services are important not only for the identification of genetic syndromes by dysmorphic examination but also for providing genetic counseling for families having possible risks and planning future pregnancies. In this review, the most common congenital anomalies in pediatric surgery were discussed as well as their genetic basis, diagnosis, prognosis and treatment options in the light of up-to-date literature.Konjenital anomaliler, tüm doğumların %3-4’ünde görülen, perinatal mortalite ve morbidite nedeni olan önemli gelişimsel defektlerdir. Sıklıkla yenidoğan dönemi ve sonrasında bu anomalilerden biri veya daha fazlasının saptanması durumunda, öncelikle bunların sınıflandırılarak olası tedavi seçeneklerini hızlı bir biçimde gözden geçirmek gerekir. Bu aşamada Pediatrik Cerrahi Anabilim Dalı çoğu zaman devreye girmekte ve bu anomalilerin düzeltilmesine katkıda bulunmaktadır. Genetik servisleri ise bu gibi olgularda dismorfolojik muayene ile olası bir genetik sendromun tanımlanmasının yanısıra özellikle daha sonra olacak gebeliklerdeki risklerin belirtildiği genetik danışmanlık sürecinde aileler için büyük öneme sahiptir. Bu derlemede, Pediatrik Cerrahi alanında sık karşılaşılan konjenital anomaliler ve bunların genetik temelleri, tanı, tedavi ve prognoz açısından yeni yaklaşımların güncel literatür bilgileriyle sistematik bir şekilde sunulması amaçlanmıştır

The molecular mechanisms of mitosis and meiosis: Review

WOS: 000254582800014In order to understand the function of the cell, which is the basic unit of human organism, the fundamentals of cell replication should be elucidated. Cell cycle checkpoints work in balance during the cell division process. The most important step in cell replication is to copy its own genetic material. During replication, mitosis lasts only I hour whereas 95% of the cell cycle process comprises the interphase. G1, S, G2 and M phases of the cell cycle are strictly controlled by the cell itself. Cell cycle checkpoints are sensitive to and control the errors that occur during the replication process, misegregation of the chromosomes, errors in DNA replication and any other errors that can occur during replication, thus maintaining the cell cycle. The molecules that have a role in the cell cycle and mitosis such as MPF (maturation promoting factor), cyclines and cell cycle inhibitors have very important functions, and proper maintenance of the cell cycle depends on the interaction between them. On the other hand, interaction between the different growth factors and cyclins during the switch to silent phase, the cell cycle inhibitors (p21 and TGF-beta) during the termination of the cell cycle, and the tumor suppressor genes (p53 and Rb) have major roles in the maintenance of the cell cycle. DNA packaging, chromosome condensation, formation of mitotic spindle and cytokinesis are under control during mitosis. In this review, the steps in mitosis and meiosis, the control points and the functions of major modulator molecules during the cell cycle are broadly reviewed with referral to recent findings

A case of acute lymphoblastic leukemia with additional chromosomes X and 5 associated with a Philadelphia chromosome in the bone marrow

WOS: 000286303200012PubMed ID: 27263746We report herein a very rare case of acute lymphoblastic leukemia having a chromosomal constitution of 48,XY,+X,+5,t(9;22)(q34;q11) in the bone marrow. A patient with additional chromosomes X and 5 with a Philadelphia chromosome has not been reported previously. However, no abnormal karyotype was obtained from the lymphocytes in our patient, and he did not have the characteristics of Klinefelter syndrome. He achieved a complete remission with IDA-FLAG and dasatinib therapy. The mechanism of trisomy 5 or any other chromosomal aneuploidy in the pathogenesis of leukemogenesis remains unclear. Further studies involving the genes affected by this karyotype and their products may lead to strategies to further increase the understanding of drug-resistant acute lymphoblastic leukemia and may represent the next frontier in the targeted therapy of those patients. (Turk J Hematol 2010; 27: 299-302

The association of RANK gene C421T and C575T polymorphisms with bone mineral density in postmenopausal Turkish women

WOS: 000324635900028PubMed ID: 23553199To investigate the association between C421T polymorphism within exon 4, C575T polymorphism within exon 6 of the RANK gene and bone mineral density (BMD) variations in postmenopausal Turkish women. One hundred seventy-eight postmenopausal women (patients = 100 and controls = 78) who applied to Ege University Faculty of Medicine, Department of Physical Medicine and Rehabilitation, for osteoporosis examination were analyzed. BMDs of the lumbar spine and femoral sites were measured. Patient and control groups were established based on their T-score values being above and/or below -1. After venous blood sampling, C421T and C575T polymorphisms of the RANK gene were assessed through PCR process following DNA extraction. Genotype frequencies for the C421T and C575T polymorphisms were compared between the control group and the patient group. No significant difference was detected between the two groups for both polymorphisms. There was also no significant difference between the control and patient groups in terms of the combined genotype (p = 0.752) and the combined haplotype analysis of the C421T and C575T polymorphisms (p = 0.723). In the control and patient groups separately, no significant differences in BMD values either at the femoral sites or at the lumbar spine were detected between the combined genotypes of the two polymorphisms. The genotypes, combined genotypes and allele frequencies of C421T and C575T polymorphisms of the RANK gene have not been found to be associated with BMD in Turkish women. Further studies including both sexes and more cases are required.Turkish Osteoporosis SocietyThis study was supported financially by Turkish Osteoporosis Society