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ABSTRACT Fragile X syndrome is considered the main known cause of inherited learning disabilities and it is characterized by mutations in the FMR1 gene. Our aim was to report an unexpected detection of a patient with fragile X syndrome by GTG-Banding karyotype analysis (G-bands after trypsin and Giemsa). The karyotype analysis identified Xq27.3 fragility in 17% of the metaphases analyzed and in 54% when using TC 199, consistent with the cytogenetic diagnosis of the syndrome. This case was the sole one to present the fra(X) tests in the high-resolution karyotype analysis in our care service, contributing to future diagnoses of patients with history of developmental delay.
RESUMO A síndrome do X frágil é a principal causa conhecida de deficiência de aprendizagem herdada, caracterizada por mutações no gene FMR1. Relatamos a detecção inesperada de um paciente com síndrome do X frágil por meio de cariótipo de sangue periférico com bandamento GTG (bandamento G após tripsina e Giemsa). A análise cariotípica identificou fragilidade Xq27.3 em 17% das metáfases analisadas e em 54% quando utilizado TC 199, consistente com o diagnóstico citogenético da síndrome. Este caso foi o único a apresentar as provas de fra(X) no cariótipo de alta resolução em nosso serviço de atendimento, contribuindo para futuros diagnósticos de pacientes com história de atraso no desenvolvimento.
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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.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Bipolar Disorder/genetics , Chromosome Fragile Sites/drug effects , Chromosome Fragility/drug effects , Chromosomes, Human/genetics , Cytogenetics , Folic Acid/pharmacology , Genetic Predisposition to DiseaseABSTRACT
Fragile sites (FS) are chromosomal regions where the normal compactation of chromatine is not observed. FRAXA (Fra Xq27.3, X sexual chromosome) is one of the most studied FS in humans. FRAXA is an expansion of the trinucleotide CGG located in the gene FMR-1. In cattle, sites of chromosomal fragility were reported in BTAX, associated with different pathologies and fertility impairment. Chromosomal microdissection has became a valuable tool for isolating chromatine fragments. In this work, it was combined the chromosomal microdissection technique with DOP-PCR in order to carry out a molecular analysis of the fragile chromosomal region BTAXq31-34. In that region, polymorphic DNA-RAPD sequences (GC rich) are present and sequences of the gene FMR-1 are missing. The results showed the usefulness of the microdissection-DOP-PCR technique for molecular characterization of fragile chromosomal sites in cattle.
Os sítios frágeis (FS) são regiões de cromossomo onde a compactação normal da cromatina não é realizada. O FRAXA (Fra Xq27.3, cromossomo sexual X) é um dos FS mais estudados em seres humanos. O FRAXA apresenta expansão do trinucleotídeo CGG localizado no gene FMR-1. Em bovinos, existem estudos informando sobre fragilidade cromossômica em BTAX associada com diversas patologias e alterações na fertilidade. A microdissecação cromossômica é uma valiosa técnica para isolar fragmentos de cromatina. Neste trabalho, combinou-se a técnica de microdissecação de cromossomo com DOP-PCR para executar a análise molecular da região do sitio frágil cromossômico BTAXq31-34. Naquela região estão presentes seqüências do polimorfo DNA-RAPD (rico em GC), em que as seqüências do gene FMR-1 estão ausentes. Os resultados mostram a utilidade da técnica de microdissecação-DOP-PCR para a caracterização molecular de sítios frágeis cromossômicos em bovinos.
Subject(s)
Animals , Cattle , Chromosome Fragile Sites , Chromatin/isolation & purification , Microdissection/methods , Microdissection/veterinary , X ChromosomeABSTRACT
0.05).⑥ The incidence of MSI at D3S1234,D3S4103,D3S1300 in recurring cases was 83.33 %,but the ratio of MSI inprimary cases was 30.77 %,the former was remarkablyhigher than the latter(P=0.004).CONCLUSION ①Microsatellite analysis showed that both LOH andMSI of FHIT gene existed in laryngeal carcinoma andhypopharyngeal carcinoma,the former was morecommon.② FHIT gene participates the developmenof laryngeal carcinoma and hypopharyngeal carcinoma and may be one of the candidate tumor suppressor genes.③ MSI of FHIT gene may be correlated with recurrence of laryngeal and hypopharyngeal carcinoma.
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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.
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Case-Control Studies , Cytogenetic Analysis , Fragile X Syndrome/genetics , Intellectual Disability/genetics , TurkeyABSTRACT
An aphidicolin is a chemical agent which selectively inhibits DNA polymerase alpha in S phase of cell cycle. The purpose of this study is toinvestigate of chromosomal abnormalities including fragile sites induced by 0.2 microgram/ml and 0.4 ng/ml aphidicolin in lymphocyte cultures of six healthy individuals. The results were follows. 1. A significant decreasing in mitotic indexes in respect to control culture was observed with both aphidicolin concentrations used. 2. The cells showing chromosome aberrations and the total number of cytogeneticic alterations were significantly increased both aphidicolin treated cultures than control cultures. 3. The total numbers of chromosomal aberrations were increased in the concentration of 0.4 microgram/ml aphidicolin compared to 0.2 microgram/ml treated groups. 4. The most frequent type of chromosomal aberration is a gap. 5. A site showing a gap or break was defined as common fragile sites (c-fra) if it appeared more than 1% of cells analyzed and in at least three of six individuals studied with the same culture treatment. Using these criteria, 3p14, 4q12, 5p13, 6q16, 9p13, and 16q23 were induced in different proportions by different concentration of aphidicolin and four of these c-fras, 4q12, 5p13, 6q16, 9p13 have not been reported so far. This results support that aphidicolin induced fragile sites differently according to cultured cell or cultured conditions, and also suggest the mechanism that common fragile sites caused be closely related with the defect of DNA synthesis in the S phase of cell cycle.
Subject(s)
Humans , Aphidicolin , Cell Cycle , Cells, Cultured , Chromosome Aberrations , Cytogenetics , DNA , DNA Polymerase I , Lymphocytes , Mitotic Index , S PhaseABSTRACT
To investigate fragile sites induced by aphidicolin which is a specific inhibitor of eukaryotic DNA polymerase a which is primarily associated with chromosomal DNA replication in human lymphocytes, HaCat cells (human keratinocytes) and MRC-5 cells (human embryonic lung fibroblast), we cultured each cells in RPMI 1640 with 10% fetal calf serum and 2% PHA. Treatment of the cells with aphidicolin was generally carried out for the last 24 hours of culturing. The drug was dissolved in DMSO and used at final concentrations of 0.05~0.15 mg/ml, corresponding to a maximum DMSO concentration of 0.028%. Karyotypes of each cells were performed by routine method, and 50 metaphases were scored for each culture for analysis of breakage rate. Experimental cells treated with APC showed a dose dependent sensitivity and the amounts of chromosome breakage induced by APC are the highest in concentration of 0.15 mg/ml. The frequency of fragile sites on each cells appeared in MRC-5 cells, lymphocytes and HaCat cells in order. The common fragile sites on all experiments was 16q23, and the common fragile sites on embryonic cells was 1p31. It can be concluded that gene or nucleic acid which is located on 16q23 is the most important factor to induce chromosomal breakage with sensitivity to aphidicolin and 1p31 is important site to induce chromosomal breakage in embryonal cells.
Subject(s)
Humans , Aphidicolin , Chromosome Breakage , Dimethyl Sulfoxide , DNA , DNA Replication , Karyotype , Lung , Lymphocytes , MetaphaseABSTRACT
Chromosomes in peripheral blood lymphocytes of 45 patients with ovarian tumour and 10 normal subjects of control were examined. The results demonstrated that the frequencies of sister chromatid exchange (SCE), micronucleus and fragility of the malignant group were significantly higher than those of the benign group and of the controls. And the fragile sites with the highest frequencies were located between 6ql5 and 6q24. The carcinogenesis and prognosis of ovarian carcinoma were also briefly disussed
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The fragile sites was induced to express, in PHA-stimulated lymphocytes chromosome of leukemic patients by low concentrations of folic acid and thymidine in 199 medium. 12 patients and 9 normal controls were examined. The results showed that both rates of the freguencies of fragile sites and the chromosome aberrations in patients were much higher than those in normal controls (20.42% :3.30%). There was significant correlation between the two groups.We found that there are 57 Fra in chromosome. These patients carried 7 of 57 Fra, which were located at the bands of oncogenes loci and cancer breakpoints, these 7 Fra are Ip36(src2),3p24(rafl)(raf2),6p23 (krasip), 8q22(mos), 14q24(fos), 22qll(bcr), 22.ql3 (sis). This observation suggests that the fragile sites may associate with leukemia
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0.05).Serum Tg of the seventh day after taking 131 I was remarkably higher than that of the seventh day before taking 131 I ( P 0.05).Conclusions:Treatment of 131 I gives rise to some harm to chromosome of Graves′ disease patients,but the harm can be restored.Serum Tg is related to the frequency of Fra8q22.