Chromosomal variations in patients with bipolar affective disorder

The study of cytogenetic abnormalities may lead to a more accurate localization of genes related to disease. Therefore, chromosome determination could be included among the routine investigations of patients with bipolar disorder. We have examined the chromosomes of 80 patients with bipolar disorder and 30 controls by using the GTG banding technique. Random numerical and structural variations were present in 26.3% of the patients and in 10% of the controls. Of these, 57.1% and 42.9% of abnormalities had structural and numerical aberrations, respectively. Structural aberrations usually consisted of deletions, heterochromatic regions of chromosome 9, and partial trisomy of various chromosomes. Numerical chromosome anomalies were present in 9 cases (42.9%), and included trisomy 21, monosomy X, 47,XXY, marker, and acentric chromosomes. The frequency of sex chromosome changes in our populations (3.75%) was significantly increased compared to that in newborns. These regions can be the most active hotspots in the genomes of bipolar patients. The identification of such chromosomal abnormalities associated with bipolar disorder could provide important implications for further research to locate disease-related gene(s) on the chromosome(s). © The Genetics Society of Korea

Polymorphisms in NRAMP1 and MBL2 genes and their relations with tuberculosis in Turkish children [Çocukluk çagı tüberkülozunda genetik yatkınlık]

PubMedID: 21554230In this study, we aimed to determine genetic susceptibility of children group who are under follow up at outpatient and inpatient clinics or newly diagnosed pediatric tuberculosis according to healthy control group. Patient group consists of 50 cases aged between 0-18 years who are under follow up at outpatient and inpatient clinics or newly diagnosed pediatric tuberculosis between 1996-2009 in Cukurova University, Faculty of Medicine, Department of Pediatrics and the control group consists of 50 healthy cases aged between 0-18 years who have neither chronic nor acute diseases and have no history of tuberculosis contact. Analysis of NRAMP1 (D543N, 3'-UTR and INT4 loci) and MBL (codon 54 and 57) gene polymorphisms carried out in Cukurova University, Faculty of Medicine, Department of Medical Biology and Genetics. In this study comprising in total 50 individuals we did not observe any significant association with microsatellite polymorphisms at the INT4, G543A and 3-UTR loci situated in the NRAMP1 gene (p> 0.005). There was no significant difference of MBL gen frequency polimorphisms of codon 54 and 57 polimorphisms between patient and control group statistically (p> 0.05). We reported that the INT4, G543A and 3-UTR loci microsatellite polymorphisms in the NRAMP1 gene were not associated with tuberculosis. No significant associations were also observed for codons 54 and 57 in the MBL2 gene. These results shed light on the role of NRAMP1 in susceptibility to tuberculosis disease and provide a plausible explanation for NRAMP1 and MBL genetic heterogeneity in tuberculosis susceptibility

Chromosome and p63 gene analysis of an infant with ectrodactyly-split hand and foot malformation

Aim: Split hand-split foot malformation (SHFM) results from central ray reduction and presents as median clefts of the hands and feet, syndactyly, aplasia or hypoplasia of the phalanges, metacarpals and metatarsals, which are frequently associated with other phenotypic abnormalities. We aimed to investigate the genetic pathway of SHFM in a child. Materials and methods: Cytogenetic and molecular genetic analysis was performed in a 10-day-old boy with split-syndactyly hand and flat-syndactyly foot. Results: We found a complex chromosomal rearrangement including breaks in 4q12, fragility in the 9q11-13 band region and 9qh+. Cytogenetic results agree with the literature findings. The mutation analysis of the p63 gene revealed no mutation. Conclusion: The phenotype of our patient may be due to variable expressivity and penetrance of the p63 gene and to other genetic factors, or the mutation can be located in the other 4 loci for SHFM. Additional minor modifying genes, which predispose to non-syndromic cleft palate, could also contribute to the expression of the cleft palate component of the EEC syndrome. © TÜBİTAK

The reliability of maternal serum triple test in prenatal diagnosis of fetal chromosomal abnormalities of pregnant Turkish women

PubMed: 21699408Aim: The purpose of this article was to evaluate the reliability of maternal serum triple marker screening of alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol for the prenatal diagnosis of fetal chromosomal abnormalities in Turkish pregnant women. Method: Medical records were used to analyze indications of amniocentesis and quantitative fluorescent-polymerase chain reaction. Anomaly screening was performed for all patients between 13 and 22 weeks of pregnancy. A total of 1725 pregnancies with chromosomal abnormality risk according to triple test screening were accepted for fetal chromosome analysis and quantitative fluorescent-polymerase chain reaction. Results: Chromosomal aberrations were observed in 56 (3.2%) cases. About 44.6% of the abnormalities detected were numerical aberrations; however, 55.3% of the abnormalities were structural aberrations. Abnormalities detected were inversion of chromosome 9 in 20 cases, trisomy 21 in 14 cases, 46,XX/47,XX, +21 in 1 case, trisomy 18 in 2 cases, trisomy 13 in 1 case, 47,XXY, in 1 case, 45,X, in 1 case, structural abnormalities in 12 cases, and mosaic or tetraploidy in 6 cases. Conclusion: Second trimester triple test is an effective screening tool for detecting fetal Down syndrome in Turkish women. © 2011, Mary Ann Liebert, Inc

Are there fetal stem cells in the maternal brain?

Fetal cells can enter maternal blood during pregnancy but whether they can also cross the blood-brain barrier to enter the maternal brain remains poorly understood. Previous results suggest that fetal cells are summoned to repair damage to the mother's brain. If this is confirmed, it would open up new and safer avenues of treatment for brain damage caused by strokes and neural diseases. In this study, we aimed to investigate whether a baby's stem cells can enter the maternal brain during pregnancy. Deceased patients who had at least one male offspring and no history of abortion and blood transfusion were included in this study. DNA was extracted from brain tissue samples of deceased women using standard phenol-chloroform extraction and ethanol precipitation methods. Genomic DNA was screened by quantitative fluorescent-polymerase chain reaction amplification together with short tandem repeat markers specific to the Y chromosome, and 13, 18, 21 and X. Any foreign DNA residues that could be used to interpret the presence of fetal stem cells in the maternal brain were monitored. Results indicated that fetal stem cells can not cross the blood-brain barrier to enter the maternal brain

Nivolumab for relapsed or refractory Hodgkin lymphoma: Real-life experience

Background: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. Patients and methods: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. Results: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. Conclusions: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

BACKGROUND: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. PATIENTS AND METHODS: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. RESULTS: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. CONCLUSIONS: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity

Nivolumab for relapsed or refractory hodgkin lymphoma experience in Turkey

22nd Congress of the European-Hematology-Association -- JUN 22-25, 2017 -- Madrid, SPAINWOS: 000404127001176…The European Hematology Associatio