Polymorphisms in NRAMP1 and MBL2 genes and their relations with tuberculosis in Turkish children.

In 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.

The first report described as an important study: The association of mannose-binding lectin gene 2 polymorphisms in children with Down syndrome.

BACKGROUND: Mannose-binding lectin gene 2 (MBL2) plays a very important role in the first line of host immune response in Down syndrome (DS). The importance of MBL2 gene polymorphisms in children with DS is unclear, and no research has addressed MBL2 gene polymorphisms in patients with DS. This is the first report describing an important association between MBL2 gene polymorphisms and infections in children with DS. MATERIALS AND METHODS: We compared the frequency of single-nucleotide polymorphisms (SNPs) at two codons of the MBL2 gene in a cross sectional cohort of 166 children with DS and 229 controls. Polymorphisms at codons 54 (GGC→GAC) and 57 (GGA→GAA) in exon 1 of the MBL2 gene were typed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique using the restriction enzymes BshN1 (derivated from Bacillus sphaericus) and MboII (derivated from Moraxella bovis), respectively. RESULTS: MBL2 codon 54 GA genotype frequency was found to be lower in patients with DS (22.9%) than those of healthy controls (35.8%), differences were statistically significant (OR = 0.532, 95% CI = 0.339-0.836, P = 0.008). On the other hand, codon 57 polymorphism in the MBL2 gene was detected in none of the DS patients, but only one person in the control group showed codon 57 GA genotype (OR = 1.004, 95% CI = 0.996-1.013, P = 1.000). CONCLUSION: Our data provides an evidence for the first time that a homozygote or heterozygote for the variant, MBL2 alleles, is not associated with infections in patients with DS, and do not influence the incidence of infections.

Cytogenetic effects of ethanol on chronic alcohol users.

AIM: Alcoholism is a significant public health problem that is also associated with a complex genetic trait. Fragile sites (FS) are potentially informative endpoints for the study of clinical disorders. We aimed to find chromosomal damages in chronic alcohol users for the purpose of finding the correlation between alcohol and chromosomal anomalies. METHODS: The potential roles/effects of ethanol on chromosome(s) were assessed in this study by investigating its cytotoxic effects in lymphocyte cultures from chronic alcoholics and controls. RESULTS: Alcoholics revealed a significantly higher frequency of FS and chromosomal aberrations (CA), and the FS clusters in specific chromosomal regions: 1q12, 1q21, 1q32, 2p13, 2q21, 2q31, 3p14, 3p25, 3q21, 4q21, 4q31, 5q31, 6p21, 7q22, 7q32, 9q13, 9q22, 10q22, 11q23, and 12q13. We also observed a significantly greater number of numerical and structural CA in alcoholics. The most frequent exchange types were deletions and polymorphic variations. CA could be due to the cumulative effect of both alcohol and smoking. The loci 1q12, 3p25, 4q31, 6p21, and 12q13 were not reported previously in alcoholics and may be hot spots for alcoholism. The overall FS frequencies were not statistically different between smoker and non-smoker controls, but smoking significantly increased the expression of 1p36, 3q21, and 5p15 sites. These sites have important clinical significance. CONCLUSIONS: Chronic alcohol abuse and the smoking habit can lead to chromosome damages that are especially influential on oncogenic regions, which may persist for a long time, and constitute a relevant factor of risk for the development of neoplasias.

Chromosomal fragile site expression in Turkish psychiatric patients.

Chromosomal aberrations associated with psychiatric disorders may suggest regions in which to focus a search for genes predisposing to psychosis by a linkage strategy. Identification of these may be especially important given the unknown pathophysiology and the probable genetic heterogeneity of psychiatric disorders. In this study, the frequencies of folate sensitive fragile sites (FS) were compared among psychiatric disorders (e.g., schizophrenia, bipolar disorder, and other psychosis) and normal individuals. The rate of FS expression in the patients was considerably higher than in the controls. Sites 1p22, 1q21, 1q32, 2q31, 3p14, 3p25, 5q22, 5q31, 6p21, 6q21, 6q25, 7q22, 7q32, 8q22, 10q21, 11q23, 12q24, 13q32, 14q24, 16q22, 17q21, Xp22 and Xq26 were expressed more frequently in the patients. Thirty possible relevant chromosomal sites were identified in schizophrenia: 1q21, 1q32, 2p13, 2q21, 3p14, 3p25, 3q21, 5q22, 5q31, 6p21, 6q25, 6q26, 7q21, 7q22, 7q32, 8q22, 9q21, 10q21, 11q23, 12q24, 13q32, 14q24, 16q22, 17q21, Xp22, Xq22, and Xq26. Possible relevant sites were also identified in bipolar disorder: sites 1p36, 1q21, 1q32, 3p14, 3p25, 5q31, 7q22, 7q32, 11q23, 12q24, 13q32, 14q24, Xp22, and Xq26. Sites in the other psychosis group were: 1p22, 1p32, 1p36, 1q21, 1q32, 2q31, 3p14, 3p25, 5q31, 6p21, 6q21, 6q25, 6q26, 7q22, 7q32, 8q22, 10q21, 11q23, 12q13, 12q24, 13q32, 16q22, 16q24, 17q21 and Xq26. Among patient groups, there were significant differences in bands 1p32, 2p13, 2q21, 2q31, 3p14, 3p25, 5q31, 6q21, 6q26, 7q22, 7q32, 9q21, 11qq23, 12q13, 12q24, 16q24, and Xq22 between schizophrenic and bipolar patients. These regions were more frequently expressed in schizophrenic patients than in bipolar patients. The 1p22, 1p32, and 16q24 regions were significantly more frequently expressed in the other psychosis group than in the bipolar group. These interesting regions, which may harbor important genes for psychosis, have produced strong support for linkage in the majority of genome scan projects.

Chromosome aberrations in a schizophrenia population.

Cytogenetic abnormalities with schizophrenia may provide a valuable clue to the identification of target loci and successful search for major genes. We have performed chromosomal examinations by using the GTG banding technique on 134 schizophrenics. In 43 patients (32%), random numerical and structural aberrations were detected. Structural aberrations predominated and usually consisted of deletions and inversion of various chromosomes. Numerical changes were present in one or two cells in 14 cases including trizomy 21, marker and acentric chromosomes, and 47,XXY. The seven cases with pericentric inversion and enlargement of the heterochromatin region of chromosome 9 (inv(9); 9qh+) were observed in the study. The incidence (5.2%) of inv(9) and 9qh+ in our schizophrenic patients were found higher than the general population, suggesting that a susceptibility locus for schizophrenia may be located at pericentromeric region of chromosome 9. Our study have detected 1q21, 7q23, inv(9), 9qh+, 11q23, 21q22, 22q11-13 and Xp11-q13 suggested that these chromosomal lesions are prevalent in schizophrenics. The reason for this might be that these anomalies increase risk for schizophrenia in a relatively nonspecific way, such as contributing to disruption of normal embryogenesis of the nervous system.

A cytogenetic study in 120 Turkish children with intellectual disability and characteristics of fragile X syndrome.

We review the evidence for the frequency of the fragile X syndrome (FXS), other X-linked abnormalities, and other chromosomal disabilities of Turkish pediatric psychiatry outpatients with intellectual disability. Reported clinical features and genetic findings were used in cytogenetic screenings to estimate the prevalence of the fragile X (fra X) and other chromosomal aberrations in 120 patients with mental retardation, language disorders, attention deficit hyperactivity, or developmental delay, in comparison with 30 healthy children. Data on the clinical, intellectual and behavioral findings in 14 fra X positive children (11.7%) is presented. Ten of the 120 patients (8.3%) had enlargement of the heterochromatin region of chromosome 9. Other chromosomal aberrations and autosomal fragile sites (FS) were also observed. There was a statistically significant difference in the autosomal and X-linked FS between the study and control groups (p < 0.05). The tests for the fra X chromosome are likely to be of diagnostic benefit in young children with autism or developmental delay, particularly in speech, and who have large and prominent ears.

Genetic alterations of chromosomes, p53 and p16 genes in low- and high-grade bladder cancer.

A majority of patients with bladder cancer present with superficial disease and subsequently, some patients show progression to muscle invasive or metastatic disease. Bladder cancer has a complex genetic process and identification of the genetic alterations which occur during progression may lead to the understanding of the nature of the disease and provide the possibility of early treatment. The aim of the present study was to compare the structural and numerical chromosomal differences and changes in the p16 and p53 genes between low-grade (LG) and high-grade (HG) bladder cancer (BC) using cytogenetic and molecular cytogenetic methods. Between March 2009 and March 2010, cytogenetic analyses were carried out on tumor and blood samples in 34 patients with transitional cell type BC, and on blood samples of 34 healthy patients as a control group. Fluorescence in situ hybridization probes for the p16 and p53 genes were also used to screen the alterations in these genes in 32 patients with BC. The patients were divided into two groups (LG and HG) and the findings were compared. A total of 11 (32.3%) patients exhibited LGBC, 22 (64.7%) exhibited HGBC and one (3%) patient exhibited carcinoma in situ. There were no differences between the LGBC and HGBC groups according to the number of chromosomal aberrations (P=0.714); however, differences between alterations of the p16 and p53 genes were significant (P=0.002 and P=0.039). Almost all structural abnormalities were found to be located to the 1q21, 1q32, 3p21 and 5q31 regions in patients with HG tumors. In conclusion, the p16 and p53 genes were altered more prominently in patients with HG tumors compared with LG tumors. The structural abnormalities in the 1q21, 1q32, 3p21 and 5q31 regions were observed more frequently in patients with HG tumors. These regions may play significant roles in the progression of BC, but further studies are required to find candidate genes for a panel of BC.

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.

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

AIM: 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.

Alterations in p16 and p53 genes and chromosomal findings in patients with lung cancer: fluorescence in situ hybridization and cytogenetic studies.

BACKGROUND: Chromosomal aberrations and instability of gene(s) are two factors related to the genetic instability of cancer cells. A loss of the tumor-suppressor function of the genes p16 and p53 is the most common event leading to the development of human cancers. Carcinoma of the lung is the leading cause of cancer deaths in the world. Chromosomal abnormalities in lung cancer may provide a valuable clue to the identification of target loci and culminate in a successful search for the major genes. The aim of this study was to investigate (i) alterations of the p16 and p53 genes and (ii) chromosomal aberrations in patients with small cell and non-small cell lung cancer by fluorescence in situ hybridization (FISH) and cytogenetic studies. We carried out cytogenetic analysis by Giemsa-banding in 18 cases. FISH probes for the p16 and p53 genes were also used on interphase nuclei to screen the alterations in these genes in lung cancer (LC). RESULTS: We observed a high frequency of losses of the p16 - in 8/18 (44%) - and p53 - in 7/18 (39%) - genes in the cases with LC. A total of 18 patients showed predominantly numerical and structural aberrations. Among these two types, structural aberrations predominated and usually consisted of deletions, breaks, and fragilities in various chromosomes. Both structural and numerical changes were observed in almost all patients. Chromosomes 3 and 1 were found to be most frequently involved in structural abnormalities, followed by chromosomes 6, 9, and 8. Autosomal aneuploidies were also observed to be the most frequent (chromosomes 22, 19, 18, 20, 9, and 17), followed by those of the X and Y chromosomes. The expression of fragile sites was also found to be significantly higher in seven chromosomal regions: 3p14, 1q21, 1q12, 6q26, 9q13, 8q22, and 8q24. CONCLUSION: Our data confirmed that DNA damage and genomic instability may be factors contributing to the mutation profile and development of lung cancer. The patients who developed lung cancer showed a high frequency of loss of both p16 and p53, in addition to chromosomal aberrations. Tobacco could be a major carcinogenic factor in lung-cancer progression. The loss of p16 and p53, and increased incidence of autosomal aneuploidy and chromatid breaks, along with other chromosomal alterations, can contribute to the progression of the disease.

The expression of folate sensitive fragile sites in patients with bipolar disorder.

PURPOSE: Genetic factors are known to be important in the etiology of bipolar disorder (BD). The fragile sites (FSs) are a very interesting subject for the study of clinical disorders. The aim of this study was to evaluate fragile sites seen in patients with bipolar disorder and find a correlation between some fragile sites and bipolar disorder. PATIENTS AND METHODS: The frequencies of folate sensitive FSs were compared in short-term whole blood cultures from bipolar patients and from normal individuals. RESULTS: The rate of FS expression in the patients was considerably higher than in the controls (p < 0.001). Several chromosome regions including 1p36, 1q21, 1q32, 3p25, 7q22, 7q32, 11q23, 12q24, 13q32, 14q24, Xp22 and Xq26 were represented considerably more often in the patients than in the controls (p value between 0.001 to 0.036). Among these FSs, the sites 1p36, 1q21, 3p25, 7q22, 7q32, and 14q24 were not observed in other studies. CONCLUSION: These regions can be the most active of hot spots in the genomes of bipolar patients, and may harbor important genes associated with BD.

Detection of parental origin and cell stage errors of a double nondisjunction in a fetus by QF-PCR.

AIM: To investigate parental origins and cell stage errors of a double nondisjunction in a fetus. METHOD: For the determination of the most common chromosome anomalies, quantitative fluorescent polymerase chain reaction method using short tandem repeat (STR) DNA markers was applied to a fetus with abnormal ultrasonographic findings. Parental origin and cell stage errors of the trisomies were inferred by comparing the inherited STR alleles. Conventional cytogenetic technique was also applied for the confirmation of the aneuploidies. RESULTS: A double nondisjunction including chromosomes 21 and X (48,XXX,+21) was detected prenatally in the fetus. The origin of both chromosomes was maternal, and the errors were in meiosis I for 21 and meiosis II for X. Molecular results were concordant with cytogenetic results. CONCLUSION: Molecular techniques could be useful for the pre- and postnatal diagnosis of the common aneuploidies and determining its parental origin. This kind of study will improve knowledge about the mechanisms of nondisjunction and enable appropriate and rapid genetic counseling.

Inheritance of pericentric inversion in chromosome 7 through the three progenies and a newborn with congenital hydronephrosis diagnosed prenatally by fetal urine sampling.

OBJECTIVE: To report the inheritance of a pericentric inversion in chromosome 7 through the three progenies, congenital hydronephrosis, and recurrent miscarriages in an extended family. DESIGN: Case report. SETTING: Medical Faculty of Cukurova University in Turkey. PATIENT(S): Referred by obstetrics and gynecology clinic. INTERVENTION(S): Fetal urine and lymphocytic karyotype. MAIN OUTCOME MEASURE(S): Chromosomal analysis from fetal urine and peripheral blood lymphocytes were performed according to standard cytogenetic methods. RESULT(S): We assessed an extended family in which a large pericentric inversion in chromosome 7 is segregating; one of the three progenies with the karyotype 46,XY,inv(7)(p22;q22) was heterozygote for the inversion and presented with congenital hydronephrosis. His mother, mother's brother, grandfather, grandfather's brother, and his daughter were similar for the inversion. CONCLUSION(S): This case describes the further molecular characterization of these breakpoints on the short or long arm of chromosome 7(p22-q22). The inv(7) is also associated with fetal wastage and may be playing a role in the etiology of the family's miscarriages. These findings can be used in clinical genetics and may be an effective tool for reproductive guidance and genetic counseling.

Partial trisomy 1p due to paternal t(1;9) translocation in a family with recurrent miscarriages.

OBJECTIVE: To report a new case with partial trisomy 1p due to paternal t(1;9) translocation in a family with recurrent miscarriages. DESIGN: Case report. SETTING: Faculty of Medicine, Cukurova University. PATIENT(S): A couple with recurrent miscarriages, an abnormal fetus, a newborn infant, paternal grandfather and grandmother. INTERVENTION(S): Chorionic villi sampling (CVS), amniocentesis, lymphocytic karyotype, and genetic counseling. MAIN OUTCOME MEASURE(S): Chromosomal analysis of CVS, amniotic cells, and peripheral blood lymphocytes were performed according to standard cytogenetic methods using G-banding technique. RESULT(S): We determined the reproductive risk in a couple who carried a balance and an unbalanced rearrangement of chromosomes 1 and 9 in two generations of a normal father with derivative 9 karyotype. The prenatal and postnatal karyotypes of the newborn infant were the same as the father [46,XY,der(9)t(1:9)(p34.2;q34.3)]. He was also phenotypically normal. The abnormal fetus that was miscarried also had a derivative 9 [46,XY,der(9)t(1:9)(p34.2;q34.3)fat]. The der(9) contained the partial short arm of chromosome 1. Both chromosome 1 showed normal. Trisomy 1p in the fetus was the result of familial derivative 9. CONCLUSION(S): Partial trisomy is associated with fetal wastage, and may play a role in the etiology of the other miscarriages in certain families. The apparent lack of increased reproductive failure may result from the selective disadvantage of aneusomic gamets at fertilization or very early spontaneous abortions of unbalanced conceptuses. The detection of couples with chromosomal anomalies can undoubtedly help prevent the births of malformed infants. These findings would be used widely in clinical genetics and as an effective tool for genetic counseling and reproductive guidance.