Novel autopsy and genetic findings in an acardiac twin: case report and literature review

ABSTRACT Twin reversed arterial perfusion (TRAP) sequence is a rare complication of monochorionic twinning whereby a donor twin perfuses an acardiac twin via aberrant vascular anastomoses. The resulting paradoxical retrograde blood flow supplying the acardiac twin is oxygen-poor, leading to some of the most severe malformations encountered in humans. Though the first descriptions of acardiac twins date back to at least the 16th century, the pathophysiologic processes which underpin the development of TRAP sequence are still being elucidated. Theories on the pathogenesis of TRAP sequence include deficiencies intrinsic to the embryo and primary abnormalities of the placental vasculature. Autopsy studies continue to provide clues to the underlying pathogenesis of TRAP sequence, and the characterization of the spectrum of manifestations that can be observed in acardiac twins. Herein, we present the clinical, autopsy, and molecular findings in a unique case of TRAP sequence. Novel findings include a primitive cloaca-like structure and chromosomal aberrations involving 6q11.1 and 15q25.1.

Cytogenomic Profiling of Chronic Lymphocytic Leukaemia Patients Using DNA Microarray

@#Introduction: Chronic lymphocytic leukaemia (CLL) is the most frequent adult leukaemia in the Western world. The clinical presentation varies greatly, from very indolent cases to those with aggressive and fast advancing disease. This variation has significant implications for clinical approaches, therapeutic tactics, and, ultimately, survival durations from diagnosis. Acquired chromosomal aberrations play a key role in CLL aetiology. Due to difficulty to obtain abnormal metaphases for analysis, few methods such as fluorescence in-situ hybridization (FISH) and multiplex ligation-dependent probe assay (MLPA) were employed to detect chromosomal aberration however the methods are limited to specific locus only. Thus, this study is aimed to detect the chromosomal aberrations using DNA microarray platform. Methods: In this retrospective study, DNA archive obtained from 7 CLL patients which collected at diagnosis and subjected to Affymetrix CytoScan® 750K single nucleotide polymorphism (SNP) array following the manufacture procedure. The raw data obtained were analysed using the Chromosome Analysis Suite (ChAS) software (Affymetrix) using annotations of genome version GRCh38 (hg38). Result: Out of 7 patients, 4 of them showing deletion of 13q while 3 of them showing deletion of 14q in various region . Some of the deleted loci were too small (0.42-0.6Mb) to be detected by conventional cytogenetic analysis (CCA). There was also the presence of additional chromosomal aberrations that could be missed by CCA, FISH, or MLPA due to cryptic deletion or duplication that was as small as 0.4MB in size. Conclusion: The present study showed that low resolution chromosomal aberration was able to be detected using DNA microarray platform in comparison to CCA, FISH and MLPA.

Mutagenic Evaluation of Fluoxetine and Fluoxetine-Galactomannan Complex Through the Analysis of Chromosomal Aberrations in Human Peripheral Leukocytes and Salmonella typhimurium/Microssome Assay / Avaliação Mutagênica de Fluoxetina e Complexo Fluoxetina-Galactomanana Através da Análise de Aberrações Cromossômicas em Leucócitos Periféricos Humanos e em Salmonella typhimurium / Ensaio Microssômico

Objectives: The purpose of this study was to evaluate the mutagenic potential of fluoxetine and fluoxetine-galactomannan. Methods: Chromosomal aberration test and Salmonella typhimurium/microsome mutagenicity assay. Results: The results showed that fluoxetine (250 µg/mL) can cause chromosomal breaks of treated leukocytes and increase the frequency of reversion of the tester strains of S. typhimurium / microsome assay only at the highest concentration (5 mg/mL), while fluoxetine encapsulated in galactomannan did not cause these changes (leukocytes and S. typhimuriums strains). Conclusion: In summary, fluoxetine showed a mutagenic effect detectable only at high concentrations in both eukaryotic and prokaryotic models. Furthermore, the fluoxetine/galactomannan complex, in this first moment, prevented the mutagenicity attributed to fluoxetine, emphasizing that the present encapsulation process can be an alternative in preventing these effects in vitro.

Objetivos: avaliar o potencial mutagênico da fluoxetina e da fluoxetina-galactomanana. Métodos: Teste de aberração cromossômica e ensaio de mutagenicidade de Salmonella typhimurium /microssoma. Resultados: a fluoxetina (250 µg/mL) pode causar quebras cromossômicas de leucócitos tratados e aumentar a frequência de reversão das cepas testadoras de S. typhimurium /microssoma apenas na concentração mais alta (5 mg/mL), enquanto a fluoxetina encapsulada em galactomanano não causou essas alterações (leucócitos e cepas de S. typhimurium). Conclusão: a fluoxetina mostrou um efeito mutagênico detectável apenas em altas concentrações em modelos eucarióticos e procarióticos. Além disso, o complexo fluoxetina/galactomanan, neste primeiro momento, evitou a mutagenicidade atribuída à fluoxetina, ressaltando que o presente processo de encapsulamento pode ser uma alternativa na prevenção desses efeitos in vitro.

Higroma quístico retronucal como marcador de anomalías cromosómicas en el primer trimestre de la gestación - Actualización

Objetivo. Evaluar la asociación del higroma quístico retronucal (HQR) y anomalías cromosómicas fetales. Métodos. Estudio observacional retrospectivo de 323 fetos del primer trimestre con riesgo para anomalías cromosómicas diagnosticados por ecografía entre las 11 y 13,6 semanas. Resultados. De 323 fetos con riesgo para anomalías cromosómicas, se encontró 132 casos de anomalías cromosómicas (40,9%). Se identificaron 145 casos de HQR; en 64 (56,6%) se realizó biopsia de vellosidades coriales y en 81 (43,5%) amniocentesis, hallándose cariotipo anómalo en 82 (56,6%). De 88 fetos con HQR aislado, 33 casos (37,5%) tuvieron alguna anomalía cromosómica; en 58 fetos con HQR asociado a otros hallazgos anormales, se encontró que en 43 fetos (74,1%) hubo anomalías cromosómicas, y de ellos 24 (41,4%) tenían onda de flujo (OVF) anormal del ductus venoso, 17 (29,3%) tenían edema generalizado, 8 casos (13,8%) con cardiopatía, 7 (12,1%) ausencia del hueso nasal. Los valores predictivos del HQR fueron: sensibilidad (S) 62,1%, especificidad (E) 67%, valor predictivo positivo (VPP) 56,6%, valor predictivo negativo (VPN) 71,9%, p<0,001, OR: 3,3. El HQR asociado a otros hallazgos anormales, tuvo los siguientes valores predictivos: S 52,4%, E 76,2%, VPP 76,2%, OR: 3,5, LR+: 2,2, p<0,000. El edema generalizado y el ductus venoso anormal tuvieron los valores predictivos más altos: VPP 88,2% y 83,3%, respectivamente. Las anomalías cromosómicas encontradas con mayor frecuencia fueron: T21 (53,7%), monosomía X (18,3%), T18 (15,9%), T13 (6,1%). Conclusiones. El higroma quístico retronucal es un marcador de riesgo con alto valor predictivo para anomalías cromosómicas, siendo mayor cuando está asociado a otros hallazgos ecográficos anormales. La identificación ecográfica del HQR en el tamizaje prenatal del primer trimestre debería ser indicación para recomendar una prueba diagnóstica para anomalías cromosómicas.

Objective: To evaluate the association of retronucal cystic hygroma (RCH) and fetal chromosomal abnormalities. Methods: Retrospective observational study of 323 first trimester fetuses at risk for chromosomal abnormalities diagnosed by ultrasound between 11 and 13.6 weeks. Results: Of 323 fetuses at risk for chromosomal abnormalities, 132 cases of chromosomal abnormalities were found (40.9%). A total of 145 cases of RCH were identified; chorionic villus biopsy was performed in 64 (56.6%) and amniocentesis in 81 (43.5%); an abnormal karyotype was found in 82 (56.6%). Of 88 fetuses with isolated RCH, 33 (37.5%) had some chromosomal abnormality. In 58 fetuses with RCH associated with other abnormal findings, chromosomal abnormalities were found in 43 fetuses (74.1%) and of these 24 (41.4%) had abnormal ductus venosus flow wave (DVF), 17 (29.3%) had generalized edema, 8 cases (13.8%) with cardiopathy, 7 (12,1%) with absent nasal bone. The predictive values of RCH were sensitivity (S) 62.1%, specificity (Sp) 67%, positive predictive value (PPV) 56.6%, negative predictive value (NPV) 71.9%, p<0.001, OR: 3.3. RCH associated with other abnormal findings were S 52.4%, Sp 76.2%, PPV 76.2%, OR: 3.5, LR+: 2.2, p<0.000. Generalized edema and abnormal ductus venosus had the highest predictive values: PPV 88.2% and 83.3%, respectively. The most frequently found chromosomal abnormalities were T21 (53.7%), monosomy X (18.3%), T18 (15.9%), T13 (6.1%). Conclusions: Retronucal cystic hygroma is a risk marker with high predictive value for chromosomal abnormalities, being higher when associated with other abnormal ultrasound findings. Ultrasonographic identification of RCH in first trimester prenatal screening should be an indication to recommend diagnostic testing for chromosomal abnormalities.

Analysis of chromosome aberration in peripheral blood lymphocytes of underground miners in non-uranium metal mines / 中华放射医学与防护杂志

Objective:To investigate chromosomal aberrations in peripheral blood lymphocytes of underground miners, in order to explore the influencing factors involved in chromosomal aberration levels of non-uranium metal mines.Methods:Totall 135 workers were recruited from an iron mine and a gold mine located in different cities of Henan province, where 69 workers worked aboveground and 66 miners worked underground in the metal mines. The radon concentration in the mines was measured by solid-state nuclear track detectors. Chromosomal aberrations in peripheral blood lymphocytes from the subjects were detected using conventional analysis method, and the influence factors of chromosomal aberrations were analyzed.Results:Radon concentration was 30-2 943 Bq/m 3 in the aboveground workplace of the mines, and 62-28 314 Bq/m 3 in underground. The age of the underground group was obviously lower than that of the aboveground group( t=2.12, P<0.05), but the frequencies of dicentrics, translocation, acentric fragment, and total chromosome-type aberrations in the underground group were significantly higher than those in the aboveground group ( χ2=10.49, 16.74, 8.15, 29.50, P<0.01). Consistent results were obtained when only male workers were regarded as object of observation ( χ2=8.44, 11.63, 4.94, 20.81, P<0.05). The frequency of translocation ( χ2=8.44, P<0.05) was dependent on the length of service in the underground group. Poisson regression analysis indicated that the aboveground and undergroud grouping partly affected the levels of dicentrics, translocation, acentric fragment, and total chromosome-type aberrations (the underground group IRR=3.25, 2.69, 1.97, 2.18, P<0.05). Conclusions:The radon exposure in the underground workplace of the metal mines may be the main factor resulting in the increase of chromosome-type aberrations of miners. The occupational health and safety of the miners who may be exposed to high radon levels are worthy of great attention.

Evidence of cytogenetic and histological damage in specimens of Astyanax lacustris (Pisces, Characidae) exposed to the hydrogen cyanide-based herbicide Dormex®

The herbicide Dormex®, a solution of hydrogen cyanamide, is a growth regulator capable of breaking the dormancy of fruit plants, and is commonly applied in agriculture. However, the biological effects of this product on non-target organisms are unknown. The present study investigated the biological response of Astyanax lacustris (Lütken, 1875) specimens exposed to Dormex® using a chromosome aberration test, the mitotic index, and the histological analysis of the gills. Forty specimens of Astyanax lacustris were obtained from a local breeding facility and divided into 10 groups (nine experimental and one control) with four fish in each aquarium (group). The control group was maintained for 24 hours in dechlorinated water while the experimental groups were allocated to one of nine different treatments, with three concentrations of Dormex®, 0.05, 0.1 and 0.5 mL L-1, and exposure for 24, 48 and 72 hours. The fish exposed to Dormex® presented chromosomal aberrations of a number of types, including chromosomal breaks, acentric fragments, decondensation, and gaps at the three Dormex® concentrations, at all exposure times. The mitotic index decreased significantly in comparison with the control group. The histological preparations of the gills revealed alterations such as hyperplasia, and lamellar fusion and edema, whereas in the control group the structure of the gills was preserved. The cytogenetic analysis revealed the genotoxic potential of the herbicide Dormex® and the morphological alterations of the gills demonstrated the sensitivity of the fish, which responded rapidly to the stressor. These findings reinforce the need for special care and restrictions on the use of these herbicides in agricultural areas located near aquatic environments.

The association between the two more common genetic causes of spermatogenic failure: a 7-year retrospective study / 亚洲男科学杂志(英文版)

Chromosomal abnormalities and Y chromosome microdeletions are considered to be the two more common genetic causes of spermatogenic failure. However, the relationship between chromosomal aberrations and Y chromosome microdeletions is still unclear. This study was to investigate the incidence and characteristics of chromosomal aberrations and Y chromosome microdeletions in infertile men, and to explore whether there was a correlation between the two genetic defects of spermatogenic failure. A 7-year retrospective study was conducted on 5465 infertile men with nonobstructive azoospermia or oligozoospermia. Karyotype analysis of peripheral blood lymphocytes was performed by standard G-banding techniques. Y chromosome microdeletions were screened by multiplex PCR amplification with six specific sequence-tagged site (STS) markers. Among the 5465 infertile men analyzed, 371 (6.8%) had Y chromosome microdeletions and the prevalence of microdeletions in azoospermia was 10.5% (259/2474) and in severe oligozoospermia was 6.3% (107/1705). A total of 4003 (73.2%) infertile men underwent karyotyping; 370 (9.2%) had chromosomal abnormalities and 222 (5.5%) had chromosomal polymorphisms. Karyotype analysis was performed on 272 (73.3%) patients with Y chromosome microdeletions and 77 (28.3%) had chromosomal aberrations, all of which involved sex chromosomes but not autosomes. There was a significant difference in the frequency of chromosomal abnormalities between men with and without Y chromosome microdeletions (P< 0.05).

Cytotoxic, clastogenic and genotoxic effects of cis-tetraammine(oxalato)ruthenium(III) dithionate on human peripheral blood lymphocytes

There is a concern about stablishing the clinical risk of drugs used for cancer treatment. In this study, the cytotoxic, clastogenic and genotoxic properties of cis-tetraammine(oxalato)ruthenium(III) dithionite - cis-[Ru(C2O4)(NH3)4]2(S2O6), were evaluated in vitro in human lymphocytes. The mitotic index (MI), chromosomal aberrations (CA) and DNA damage by comet assay were also analyzed. The MTT test revealed that the ruthenium compound showed a slight cytotoxic effect at the highest concentration tested. The IC50 value for the compound after 24 hours of exposure was 185.4 µM. The MI values of human peripheral blood lymphocytes treated with 0.015, 0.15, 1.5 and 150 µM of cis-[Ru(C2O4)(NH3)4]2(S2O6) were 6.1, 3.9, 3.2 and 0.2%, respectively. The lowest concentration, 0.015 µM, did not show any cytotoxic activity. The CA values for the 0.015, 0.15 and 1.5 µM concentrations presented low frequency (1.5, 1.6 and 2.3%, respectively), and did not express clastogenic activity when compared to the negative control, although it was observed clastogenic activity in the highest concentration tested (150 µM). The results obtained by the comet assay suggest that this compound does not present genotoxic activity at lower concentrations. The results show that cis-[Ru(C2O4)(NH3)4]2(S2O6) has no cytotoxic, clastogenic or genotoxic in vitro effects at concentrations less than or equal to 0.015 µM. This information proves as promising in the treatment of cancer and is crucial for future trials.

Application of Veterinary Cytogenetics in Domestic Animals: A Review

Cytogenetics is the study of chromosomes; their structure and properties, chromosome behavior during cell division, their influence on traits and factors which cause changes in chromosomes. Veterinary cytogenetics is the application of cytogenetics to clinical problems that occur in animal production. It has been applied to understand problems such as infertility and its types, embryonic and fetal death, abnormality in sexual and somatic development and hybrid sterility and also prenatal sex determination and other forms of chromosomal abnormalities. These are achieved through conventional and banded karyotyping techniques and molecular cytogenetic techniques. Although conventional techniques are still useful and very widely applied, the nature of cytogenetics has gradually changed as a result of advances achieved in the molecular cytogenetic techniques for example fluorescent in situ hybridization and array-based techniques. These changes are evident in both molecular diagnostics and basic research. The combination of conventional and molecular cytogenetics has given rise to high resolution techniques which have enabled the study of fundamental questions regarding biological processes. It enables the study of inherited syndromes, the mechanisms of tumorigenesis at molecular level, genome organization and the determination of chromosome homologies between species. It allows the ease with which animals are selected in breeding programs and other important aspects of animal production. In this paper we discussed a number of techniques employed in cytogenetics and their methodologies, and recommend where future focus should be for the benefits of animal production.

Fetal pulmonary atresia with ventricular septal defect :echocardiographic findings ,associated anomalies and chromosomal characteristics / 中华超声影像学杂志

Objective To analyze the echocardiographic findings , associated anomalies and chromosomal characteristics in fetuses with pulmonary atresia with ventricular septal defect ( PA/VSD ) . Methods T he echocardiographic data and follow‐up materials were retrospectively reviewed in 30 256 fetuses from December 2012 to M arch 2018 in the consultation center of fetal heart disease in maternal‐fetal medicine in Anzhen hospital . Of all the fetuses ,59 cases ( 0 .19% ) had PA/VSD . T he echocardiographic findings ,associated anomalies and chromosomal characteristics were retrospectively analyzed in all the 59 fetuses with PA/VSD . Based on w hether the presence of the native pulmonary arteries and the major aortopulmonary collateral arteries ( M APCAs) or not ,the PA‐VSD was classified into type A ,type B ,and type C . Results A large ventricular defect was demonstrated in five‐chamber view with 61 .7% of the mean ratio of the aortic overriding . O ther fetal echocardiographic features of all the 59 fetuses with PA/VSD included :the right aortic arch ( n ＝19 ) ,reversal flow in the ductus arteriosus ( n ＝40 ) ,M APCAs ( n ＝24) . T he classification of the PA/VSD included :type A ( n ＝35) ,type B ( n ＝5) and type C ( n ＝19) . Associated anomalies :persistent left superior vena cava ( n ＝ 13 ) ,anomalous pulmonary vein connection ( n＝5 ) ,complete atrioventricular septal defect ( n ＝ 5 ) ; single umbilical artery ( n ＝ 3 ) ,right atrial isomerism ( n ＝3) . Of all the 30 cases performed chromosomal test ,3 cases had aneuploidy and 7 cases had microdeletion of chromosome . Conclusions The fetal echocardiographic findings of the PA/VSD are characteristic . For prenatal diagnosis of PA/VSD ,the type of PA/VSD should be defined and chromosomal test should be performed ,w hich can be helpful for prenatal consulting .

Epidemiological and cytogenetic profiles of patients with hematological malignancies and their relationship with aging

ABSTRACT Background: Hematologic neoplasms are associated with mutations in hematopoietic cells and chromosomal abnormalities. During aging, about 2-3% of the elderly have chromosomal abnormalities arising from clonal mosaicism, the immune system is impaired and the bone marrow loses its ability to replace blood cells. Objective: To describe the epidemiological and cytogenetic profile of hematological malignancies, highlighting the frequency of chromosomal alterations in these neoplasms associated with aging. Method: A retrospective cross-sectional study with analysis of karyotype exams results was performed in the Cytogenetic Laboratory of thee Blood Center of the Faculdade de Medicina de Marilia (FAMEMA) between 1998 and 2016. Blood samples from child and adult patients with different hematological malignancies treated in the Onco-hematology Outpatient Clinics of the local blood center and hospitals, and external clinics were tested. Results: Karyotype exam results of 746 patients with a mean age of 54.7 years (±23.1) were analyzed. The elderly had the highest frequency of hematological malignancies (50.9%), followed by adults (38.3%) and young people (10.7%); elderly women had the highest percentage (55.0%). Normal karyotypes (46,XX/46,XY) were more common (61.8%) compared to abnormal karyotypes, especially among the elderly (56.4%). Myeloproliferative neoplasms were an exception with 67.4% of abnormal karyotypes. Conclusion: There is a higher frequency of hematological malignancies among the elderly. It is possible to conclude that failures in genomic mechanisms and hematopoiesis with aging lead to the formation of cells with the chromosomal alterations found in hematological malignancies.

Chromosomal aberrations in multiple myeloma: A study on Indian population

Aims: The aim of this study was to evaluate the complexity of the chromosomal abnormalities in multiple myeloma (MM) cases and to correlate the findings with the previous reported cases. Materials and Methods: Bone marrow samples were obtained from patients with MM and sent for cytogenetic study. The patient's details were logged and the cytogenetic test was performed. The karyotypes were analyzed and interpreted as per the standard guidelines. Results: Of the compiled data of cases from 2013 to 2016, 34 patients were diagnosed with MM. About 15% were below the age of 50, maximum patients were between ages of 61 and 70 years (50%). There were 25 male and 9 female. Twenty-one cases had normal karyotypes and few cases showed structural rearrangements and numerical abnormalities. Conclusions: From the data compiled, only a total of 34 cases were positive for MM, indicating that the disease is quite rare in our population. It has been previously reported that the disease usually occurs in people over the age of 50 years, however, in this study, 5 (15%) were below the age of 50 indicating that MM can affect the age group below 50 years as well. The numerical, structural abnormalities and few clonal abnormalities observed in our study added a few more to the previously reported abnormalities. However, the interesting finding of our study was a case with a combination of clones of hypodiploidy, hyperdiploidy, hypotetraploidy, and hypertetraploidy which was in contrary to the reported literatures, which were only one type of ploidy were observed. Thus, the heterogeneity and complexity of the chromosomal abnormalities in MM and the challenge in staging the disease have been proven in our study.

Effect Of Synthetic Progesterone (norethisterone) On Human Chromosomes: A Cytogenetic Study From India

Birth restriction methods dates back to prehistoric times, half a million years ago. Modern contraceptive methodsconstitute most contraceptive use. Nearly 800 million married or in-union women are projected to be usingcontraception in 2030. Norethisterone (synthetic progesterone) is used for many therapeutic purposes, and isbeing used by millions of women in India. The present study was carried out during August 2009 to July 2011 onsixty fertile females within reproductive age group. Chromosomal analysis was carried out to find the effects ofsynthetic progesterone (Norethisterone) on human chromosomes in lymphocyte culture in vitro in three groups at0, 75 µg, 100 µg of drug per ml respectively and observed for chromosomal aberrations like break, gap, dicentricchromosome and chromosomal association. Chromosomal aberrations were significantly increased at higherconcentrations. Mean chromosomal gaps at 0µg/ml, 75µg/ml and 100 µg/ml concentration were 6.90, 7.62 and10.58 respectively and mean chromosomal breaks in that same concentration were 6.63, 7.28 and 10.08respectively. 30 samples of the 60 showed chromosomal associations and 5 showed dicentric chromosomes.There is a direct correlation between increase in concentration of Norethisterone and structural chromosomalaberrations, which may be carried to next generation, and lead to anomalies in progeny of woman taking suchhigh doses of synthetic progesterone

The current research status on chromosomal aberrations of radiation workers / 中华放射医学与防护杂志

Long-term exposure to low dose ionizing radiation contributes to the damage of radiosensitive tissue and organ in radiation workers.The main cytogenetic index used to evaluate radiation damage induced by chronic low dose ionizing radiation is the chromosome aberrations of peripheral blood lymphocytes.In this paper,the cytogenetic evaluation indicators of radiation workers exposed to low dose ionizing radiation were reviewed basing on the research achievements of domestic and foreign scholars.The goals of this review were to supply the present situation and limitation of chromosomal aberration analysis in peripheral blood lymphocytes of radiation workers and to provide a reference for the chromosomal aberration test and assessment of radiation workers in China.

Follow-up of radiosensitive tissues in children with congenital heart disease treated by interventional operation / 中华放射医学与防护杂志

Objective To understand effects of the interventional operation on thyroid,peripheral blood indexes and chromosomal aberrations (CA) of peripheral lymphocyte of children with congenital heart disease (CHD).Methods Follow-up studies were conducted in 70 child patients undergoing cardiac catheterization and 23 with open heart surgery as control from 2010 to 2013.Postoperative follow-up examinations included thyroid ultrasound,blood routine indexes and analyses of CAs.Results Difference in thyroid ultrasound abnormality rate was not statistically significant between children with cardiac catheterization and control group (40.0％ vs.43.5％,P ＞ 0.05).There was no significant difference in white blood cell (WBC) count between interventional group and control group (P ＞ 0.05).The effects of disease type and operation time on thyroid ultrasound and WBC count were not observed (P ＞ 0.05).The frequency of chromosome aberrations,including acentric fragment,dicentrics and translocation in interventional group [(0.76 ± 0.07) ％],was higher than in control group [(0.25 ± 0.07) ％,(Z =-3.631,P ＜ 0.05],and the rates of acentric fragment and translocation were also higher in interventional group (Z =-2.531,-2.397,P ＜ 0.05).Conclusions Effect of intervention therapy on thyroid structure and WBC count in children with CHD was not observed,but the genotoxic effects remain in children with cardiac catheterization.

Alterações respiratórias, auditivas e citogenéticas em trabalhadores de um estaleiro no Rio de Janeiro: estudo de caso / Respiratory, audiologic and cytogenetic alterations in workers of a shipyard in Rio de Janeiro: case study

Resumo Introdução Este estudo avaliou alterações respiratórias, auditivas e citogenéticas em trabalhadores de um estaleiro em Angra dos Reis, no Estado do Rio de Janeiro, relacionadas à exposição de pintores a solventes, metais e ruído no ambiente de trabalho. Métodos Foram avaliados função pulmonar, perdas auditivas e índice de reconhecimento da fala, e alterações citogenéticas pelo teste de aberrações cromossômicas. Foram avaliados manganês e chumbo em sangue por espectrometria de absorção atômica. Os indicadores de efeito utilizados para chumbo foram ALAD e ALA-U, determinados por espectrofotometria e cromatografia líquida, respectivamente. Resultados Seis dos 9 trabalhadores avaliados apresentaram alteração funcional respiratória. Quase 70% dos 18 trabalhadores avaliados apresentaram audição reduzida, com associação entre PAIR e chumbo em sangue. O percentual médio de recuperação da ALAD foi de 32,9%, com médias de ALA-U de 1,7 mg g-1 creatinina, 4,65 µg dL-1 para Pb-S e 10 µg L -1 para Mn-S entre os trabalhadores. Foram observadas associações entre ALA-D ativada com Mn-S e com a presença de aberrações cromossômicas. As alterações citogenéticas identificadas foram aneuploidias, separação prematura centromérica e aberrações como formação de anéis, quebras e união de cromátides irmãs. Conclusão os trabalhadores do estaleiro apresentam alterações que podem ser associadas à exposição ocupacional.

Abstract Introduction This study evaluated respiratory, audiological and cytogenetic alterations in shipyard workers in Angra dos Reis, state of Rio de Janeiro/Brazil, and their correlation to the occupational exposure of painters to solvents, metals and noise present. Methods We evaluated pulmonary function, hearing loss and speech recognition, as well as cytogenetic alterations. Indicators of exposure to lead and manganese in blood were evaluated by atomic absorption spectrometry. The determination of ALAD and ALA-U was performed by spectrophotometry and liquid chromatography, respectively. Results Six of the 9 workers evaluated for lung function had respiratory functional impairment. Almost 70% of the 18 evaluated workers had reduced hearing, with association between PAIR and values of lead in blood. The average percentage of recovery of ALAD was 32.9%; average was 1.7 mg g-1 creatinine for ALA-U, 4.65 µg dL-1 for Pb-B and 10 µg L-1 for Mn-B. We observed associations between activated ALA-D with Mn-B and the presence of chromosomal aberrations. Furthermore, we identified cytogenetic alterations as aneuploidy, premature centromere separation; as well as ring formation, breakage, and sister chromatid union. Conclusion Shipyard workers presented alterations that can be associated with occupational exposure.

Identifying Mazama gouazoubira (Artiodactyla; Cervidae) chromosomes involved in rearrangements induced by doxorubicin

Abstract The process of karyotype evolution in Cervidae from a common ancestor (2n = 70, FN = 70) has been marked by complex chromosomal rearrangements. This ancestral karyotype has been retained by the current species Mazama gouazoubira (Fischer 1814), for which a chromosomal polymorphism (Robertsonian translocations and the presence of B chromosomes) has been described, presumably caused by a chromosome fragility. Thus, this study has identified doxorubicin-induced chromosome aberrations and mapped the regions involved in breaks, which may be related to the chromosome evolution process. G-banding pattern showed that 21 pairs of chromosomes presented chromosomal aberrations, 60% of the total chromosome number of the species M. gouazoubira. Among chromosomes that carry aberrations, the region where they were most frequently concentrated was distal relative to the centromere. These data suggest that certain chromosomal regions may be more susceptible to chromosome fragility and consequently could be involved in karyotype differentiation in species of the family Cervidae.

Trisomía parcial del cromosoma 13: presentación de un caso / Partial trisomy of chromosome 13: presentation of a case

Fundamento: La trisomía del cromosoma 13 es una enfermedad genética con una incidencia reportada de 1x 20 000 nacidos vivos, que resulta de la presencia de un cromosoma 13 supernumerario; es la trisomía reportada menos frecuente en la especie humana y con diferentes expresiones clínicas. Objetivo: Reportar el caso debido a su poca frecuencia y a su forma de presentación clínica. Reporte del caso: Recién nacido a término, que nace en buenas condiciones, bajo peso al nacer, con diagnóstico prenatal de trisomía parcial 13. Evolucionó tempranamente con distres respiratorio siendo necesario el uso de ventilación mecánica y convulsiones. Se retiró de la ventilación con esfuerzo respiratorio efectivo. Otra anomalía presentada fue una comunicación interauricular e insuficiencia cardiaca. Conclusiones: El pronóstico de vida en estos pacientes se relaciona claramente con la gravedad de las malformaciones y a su vez con el grado de alteración cromosómica, es esta forma de presentación la menos complicada y la de mayor sobrevida, por lo que se recomienda una atención médica de alta especialización para lograr la estabilidad de este paciente el mayor tiempo posible.

Background: Trisomy of chromosome 13 is a genetic disease with a reported incidence of 1x 20 000 live births, resulting from the presence of a supernumerary chromosome 13; is the trisomy reported less frequent in the human species and with different clinical expressions. Objective: To report the case due to its infrequency and to its clinical presentation. Case report: Newborn to term, born in good condition, underweight at birth, with prenatal diagnosis of partial trisomy 13. Early evolution with respiratory distress with the need of using the mechanical ventilation and convulsions. Ventilation was retired with effective respiratory effort. Another anomaly presented was atrial septal defect and heart failure. Conclusions: The prognosis of life in these patients is clearly related to the severity of the malformations and, in turn, to the degree of chromosomal alteration, this form of presentation is the least complicated and the one with the highest survival rate, Of high specialization to achieve the stability of this patient as long as possible.

Frecuencia de aberraciones cromosómicas en pacientes del instituto de genética-UMSA período 2011 – 2015 / Frequency of chromosomopathies at the institute of genetics-UMSA period 2011 -2015

Las anomalías cromosómicas más frecuentes son las aneuploidías, donde resaltan las trisomías autosomas 21, 18, y 13. Son un motivo frecuente de abortos espontáneos, discapacidad intelectual, recién nacidos multimalformados, infertilidad, genitales ambiguos, y juegan un importante rol en la patogenia de enfermedades malignas OBJETIVO: Determinar la frecuencia de pacientes diagnosticados con aberraciones cromosómicas en el Instituto de Genética de la Universidad Mayor de San Andrés entre los años 2011 y 2015. METODOLOGÍA: Estudio de tipo descriptivo, serie de casos. Lugar, Instituto de Genética; La Paz, Bolivia. Período 2011 ­ 2015. Población, pacientes con cariotipo realizado en el Instituto de Genética. RESULTADOS: Se realizaron un total de 1070 estudios citogenéticos, siendo euploides un 69% de los pacientes. Dentro de los cariotipos aneuploides (31%) encontramos 88% de aberraciones cromosómicas constitutivas, y 12% de adquiridas. Las cromosomopatías más frecuentes fueron la trisomía 21, monosomía del X y translocaciones. CONCLUSIONES: Las Aberraciones cromosómicas ocupan un lugar importante en la patología genética humana, representando el 0,4% de los recién nacidos vivos (1). Realizar éste trabajo de investigación nos muestra su existencia en nuestra población, y que no son sólo la letra chica de los libros o casos extraños de película. Es muy necesario tener conocimiento sobre los motivos de solicitud de cariotipo para poder realizar un diagnóstico oportuno, y poder mejorar la calidad de vida del paciente y su familia.

OBJECTIVE: To determine the frequency of patients diagnosed with chromosomal aberrations at the Genetics Institute of the Universidad Mayor de San Andrés between 2011 and 2015. METHODS: Observational, descriptive cross-sectional study. Place, Institute of Genetics; La Paz, Bolivia. Period 2011 - 2015. Population, patients with karyotype performed at the Institute of Genetics. RESULTS: A total of 1070 cytogenetic studies were performed, with 69% of patients being euploid. Within the aneuploid karyotypes (31%) we found 88% constitutive chromosomal aberrations, and 12% acquired. The most frequent chromosomopathies were trisomy 21, X monosomy and translocations. CONCLUSIONS: Chromosomal Aberrations occupy an important place in human genetic pathology, representing 0.4% of the newborns. Performing this research shows us the existence of these pathologies in our population, and that are not only the small print of books or strange cases of film. It is very necessary to have knowledge about chromosomal aberrations in order to make a timely diagnosis and to improve the quality of life of the patient and his family

The association between histone modification of H3K14ac and genetic damage in peripheral blood lymphocyte of coal-burning arsenicosis residents / 中华地方病学杂志

Objective To explore the association of H3K14 acetylation (ac) with arsenicosis induced by coal-burning and arsenic-induced genetic damage,which might help us to find an biomarker to monitor the arsenicosis and arsenic-induced toxicity.Methods Totally 151 arsenicosis subjects were recruited from Jiaole Village of Xingren County,Guizhou.According to "National Principle for Diagnosis of Arsenicosis" (WS/T 211-2001),the arsenicosis group was divided into 3 subgroups:mild poisoning (n =62),intermediate poisoning (n =50) and severe poisoning (n =39).The control group was comprised of 78 healthy villagers from Jiaole Village who were exhibited no signs of arseniasis.The hair,the urine and the peripheral blood samples were collected from the subjects.The contents of arsenic in the hair samples were analyzed with inductively coupled plasma mass spectrometry.Histones were extracted from human peripheral blood lymphocytes (PBLCs) using the method of acid extraction.The levels of H3K14ac was measured with a sandwich enzyme-linked immunosorbent assay (ELISA).The rate of micronucleus (MN) and chromosome aberration (CA) of peripheral blood lymphocytes were examined by genetic methods.The levels of urinary 8-hydroxy-2 deoxyguanosine (8-OHdG) in all the subjects were measured with the high performance liquid lhromatography-mass spectrometry (HPLC-MS).Results ①The association of arsenic-exposure with arsenicosis induced by coal-burning and H3K14ac:The levels of hair arsenic in arsenicosis group [0.27(0.15-0.39) μg/g] was significant higher than that in control group [0.15 (0.08-0.20) μg/g,F=10.736,P ＜ 0.01].The degree of arsenicosis was positive correlation with the hair-arsenic level (r =0.363,P ＜ 0.05).The levels of H3K14ac was also positive correlation with the hair-arsenic level (r =0.385,P ＜ 0.05).②The association of H3K14ac and arsenicosis induced by coal-burning:The levels of H3K14ac in arsenicosis group (4.07 ± 4.03) was 2.5-fold higher than that in control group (1.62-± 1.19,F =19.753,P ＜ 0.01).H3K14ac was a risk factor of arsenicosis,the risk of arsenicosis increased correspondingly with the levels of H3K14ac [OR (95％CI) =1.779 (1.323-2.392),P ＜ 0.01].③The correlation of H3K14ac and the degree of arsenicosis:Based on the degree of arsenicosis,we found a significant difference in the levels of H3K14ac among the four groups (F =7524,P ＜ 0.01).Compared with the non-poisoning group (1.62 ± 1.19),the levels of H3K14ac in mild poisoning,intermediate poisoning and severe poisoning subgroups (3.70 ± 3.20,4.95 ± 5.47,3.49 ± 2.62) were increased (all P ＜ 0.01),but there were no significant differences in the levels of H3K14ac between the mild poisoning,intermediate poisoning and severe poisoning subgroups (P ＞ 0.05).(④)The genetic damage of all subjects:The rate of MN (2.03 ± 1.55) and CA (12.44 ± 5.01) in arsenicosis group were significantly higher than those in control group (MN:1.17 ± 0.97,Wald =14.121;CA:6.29 ± 2.41,Wald =83.164,P ＜ 0.05).Urinary 8-OHdG was increased in arsenicosis group than that in control group [(3.80 ± 3.88),(2.33 ±1.34) μg/g Cr,F =6.116,P ＜ 0.05].⑤The association of H3K14ac with genetic damage:The results revealed that H3K14ac modification was positively correlated with the rate of CA (β =0.84,P ＜ 0.01).The level of H3K14ac was not significantly associated with the rate of MN and urinary 8-OHdG (MN:β =0.10,P ＞ 0.05;8-OHdG:β=0.05,P ＞ 0.05).Conclusions The increase of H3K14ac modification in human peripheral blood lymphocytes is a risk factor of arsenic poisoning.Additionally,the dysregulation of H3K14ac was significant association with arsenic-induced chromosomal aberrations.