Análisis citogenético en linfocitos de trabajadores expuestos a radiación ionizante en una unidad de cardiología intervencional de Chile: estudio piloto y revisión de la literatura / Citogenetic effects upon lymphocyes in subjects exposed to ionizing radiadion in an interventional laboratory cardiology: pilot study and literature review

ANTECEDENTES: Un número creciente de artículos está llamando la atención en forma consistente sobre la eventual asociación que existe entre los denominados trabajadores ocupacionalmente expuestos a bajos niveles de radiación ionizante (POEs) y una mayor frecuencia de aberraciones cromosómicas, a nivel Sudamericano estos estudios son escasos. OBJETIVO: Evaluar la frecuencia de aberraciones cromosómicas en linfocitos de sangre periférica de POEs de un hospital y de sujetos sanos. Adicionalmente, se realizó una revisión exhaustiva de los artículos que a la fecha abordaron este tema. MATERIAL Y MÉTODO: Se condujo un análisis citogenético destinado a cuantificar las aberraciones cromosómicas en sangre periférica de linfocitos de 6 POEs de la unidad de Cardiología Intervencional y, como controles, 6 muestras de sujetos de la población general fueron analizadas. RESULTADOS: Se observó un importante contraste en el número de aberraciones cromosómicas presentadas en los POEs versus la población general no expuesta a radiaciones ionizantes, siendo esta de una relación de 6:1, respectivamente. CONCLUSIÓN: Los resultados preliminares indican una mayor frecuencia de aberraciones cromosómicas en los POEs versus la población general, sin embargo, se deberá esperar los resultados de la segunda fase de investigación, donde al ampliar la muestra en análisis se podrán obtener conclusiones estadísticamente significativas.

BACKGROUND: There is growing evidence of an increased number of chromosomes aberrations in subjects exposed to low levels of ionizing radiation (POEs). There are few studies on this subject in Latin America AIM: To evaluate the frequency of chromosome aberrations in lymphocytes obtained from peripheral blood in subjects working in laboratories where low levels of ionizing radiation are present and to compare these findings to those of unexposed subjects. METHODS: A cytogenic analysis to quantify chromosome aberrations was performed in 6 POs subjects from a cardiology invasive laboratory and 6 controls from a general unexposed population. RESULTS: Compared to controls, an approximately 6-fold increase in the number of chromosome aberrations was observed.in subjects exposed to ionizing radiation CONCLUSION: These preliminary results indicate that there is an increased number of chromosome aberrations in subjects exposed to low levels of ionizing radiation, as occurs in people working in a cardiology interventional laboratory. Studies in large numbers of subjects and preferably followed prospectively are needed to evaluate more precisely this effect.

Genetic Testing and Pregnancy Outcome Analysis of 362 Fetuses with Congenital Heart Disease Identified by Prenatal Ultrasound / Análise de Teste Genético e de Desfecho da Gestação de 362 Fetos com Cardiopatia Congênita Identificados por Ultrassom Pré-Natal

Abstract Background: Congenital heart defects (CHD), as the most common congenital anomaly, have been reported to be associated with chromosomal abnormalities. Currently, patients with CHD are routinely offered karyotyping and chromosomal microarray (CMA) testing, but the genotype-phenotype relationship has not yet been fully established. Objective: To determine the type and frequency of chromosomal abnormalities in fetuses with CHD and to analyze pregnancy outcomes of fetuses with heart abnormalities caused by different genetic factors. Methods: A total of 362 cases of CHD were enrolled from 2009 to 2016. Detailed ultrasound and laboratory examinations, including karyotyping and CMA, were performed. Outcome was obtained from discharge summaries. Results: Of the 362 fetuses, 220 were found with an isolated CHD, and 142 had CHD with extracardiac anomaly. Among these 362 fetuses, 140 were identified with a genetic cause, including 111 cases with aneuploidy, 10 cases with abnormality of chromosomal structure by karyotyping and 19 cases with pathogenic or likely pathogenic copy-number variations (CNVs) by CMA. The detection rate is close to 38.7%. Only one (identified as trisomy 18 syndrome) in 140 positive cases resulted in perinatal death, with the others being induced. The remaining 222 cases had negative results for both genetic testing and of these cases, 56 resulted in induced labor, and 77 had natural childbirth or caesarean births. The pregnancy outcome of the remaining 89 cases was uncertain. Conclusions: Karyotyping and CMA are effective and accurate prenatal genetic techniques for identifying fetal chromosomal abnormalities associated with cardiac defects, and this can assist clinical doctors to perform appropriate genetic counselling with regard to the etiology and outcome of CHD.

Resumo Fundamento: As cardiopatias congênitas (CCs) são as anomalias congênitas mais comuns, e têm sido associadas a anormalidades cromossômicas. Atualmente, a cariotipagem e a análise cromossômica por microarray (CMA) são oferecidas rotineiramente aos pacientes, mas a relação genótipo-fenótipo ainda não foi totalmente estabelecida. Objetivo: Determinar o tipo e a frequência das anomalias cromossômicas em fetos com CC e analisar os desfechos da gestação de fetos com anormalidades cardíacas causadas por diferentes fatores genéticos. Métodos: No total, foram admitidos 362 casos de CC entre 2009 e 2016. Ultrassonografia e exames laboratoriais detalhados foram realizados, incluindo cariotipagem e CMA. O resultado foi obtido a partir das folhas de epicrise. Resultados: Dos 362 fetos, 220 apresentaram doença coronariana isolada e 142 apresentaram doença coronariana com anomalia extracardíaca. Entre esses 362 fetos, foram identificados 140 com causa genética, incluindo 111 casos com aneuploidia, 10 casos com anormalidade da estrutura cromossômica por cariotipagem e 19 casos com variações no número de cópias (CNVs) patogênicas ou provavelmente patogênicas por CMA. A taxa de detecção é de aproximadamente 38,7%. Apenas um (identificado como síndrome da trissomia do cromossomo 18) em 140 casos positivos resultou em morte perinatal, com as demais sendo induzidas. Os 222 casos restantes tiveram resultados negativos para ambos os testes genéticos e, destes, 56 resultaram em trabalho de parto induzido e 77 tiveram partos naturais ou cesarianas. O desfecho da gravidez dos 89 casos restantes foi incerto. Conclusões: A cariotipagem e a CMA são técnicas genéticas pré-natais eficazes e precisas para a identificação de anomalias cromossômicas fetais associadas a defeitos cardíacos, e isso pode ajudar os médicos a realizar aconselhamento genético adequado com relação à etiologia e ao desfecho das cardiopatias congênitas.

Frequency of Chromosomal Abnormalities in Products of Conception / Frequência de anomalias cromossômicas em material de aborto

Abstract Purpose To describe the frequencies of chromosomal abnormalities found in abortion material, and to observe its correlation to maternal age. Methods A retrospective study was conducted based on data obtained from the databank of a medical genetics laboratory in Belo Horizonte, MG, Brazil. A total of 884 results from products of conception analysis were included, 204 of which were analyzed by cytogenetics, and 680bymolecular biology basedon quantitative fluorescence polymerase chain reaction (QF-PCR). The frequency of individual chromosomal aberrations and the relationship between the presence of anomalies and maternal age were also evaluated. Results The conventional cytogenetics technique was able to detect 52% of normal and 48% of abnormal results in the analyzed material. Quantitative fluorescence polymerase chain reaction revealed 60% of normal and 40% of abnormal results from the samples evaluated by this method. The presence of trisomy 15 was detected only by cytogenetics, as it was not included in the QF-PCR routine investigation in the laboratory. A significant increase in abnormal results was observed among women aged 35 years or older compared with younger women (p = 0.02). Conclusion Chromosomal aberrations are still a major cause of spontaneous abortion, and the conventional cytogenetics technique is efficient for miscarriage material analysis, but molecular methods such as QF-PCR are adequate complementary strategies to detect the major chromosomal anomalies, leading to technical reports with reliable results.

Resumo Objetivos Descrever a frequência de anomalias cromossômicas encontradas em material de aborto, e observar se estas estão relacionadas com a idade materna. Métodos Foi realizado um estudo retrospectivo no banco de dados de um laboratório de genética médica em Belo Horizonte, MG. O estudo incluiu 204 resultados avaliados por citogenética, e 680 resultados por biologia molecular baseada em reação em ensaio fluorescente da reação em cadeia da polimerase (QF-PCR), totalizando um número de 884 análises. A frequência de diferentes anomalias cromossômicas e a relação entre a presença de anomalias e a idade materna também foi avaliada. Resultados A citogenética convencional foi capaz de detectar 52% de resultados normais e 48% de resultados anormais no material analisado. A QF-PCR revelou 60% de resultados normais e 40% de anormais nas amostras avaliadas por esta técnica. A presença da trissomia 15 foi detectada por citogenética,mas até então não era incluída na investigação por QF-PCR no laboratório. Umaumento significativo na quantidade de resultados anormais foi observado em mulheres comidade de 35 anos ou mais, quando comparado a mulheres mais jovens (p = 0,02). Conclusão As aberrações cromossômicas são causas importantes de abortos espontâneos, e o estudo citogenético é eficaz para a análise das amostras de material de aborto, mas as técnicas moleculares, como a QF-PCR, representam métodos complementares adequados para detectar as principais anomalias cromossômicas, possibilitando a liberação de laudos com resultados confiáveis.

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

Evaluation of a father and son with atypical chronic myeloid leukemia with SETBP1 mutations and a review of the literature

We report the case of a father and son diagnosed with atypical chronic myeloid leukemia (aCML). Both patients harbored SETBP1 mutations, which are present in 24.3% of aCML patients. Moreover, both shared the variant encoding p.Pro737His, but the aCML severity was greater in the son because of the presence of two other missense mutations causing p.Asp868Asn and p.Ser885Arg alterations. SETBP1 mutations may be associated with an adverse prognosis, so their detection would help in the diagnosis of aCML and the determination of a patient's prognosis.

Estudio citogenético en 677 casos de aborto espontáneo / Cytogenetic study of 677 spontaneous abortions

INTRODUCCIÓN: La reproducción humana es un proceso relativamente ineficaz. Los abortos espontáneos ocurren entre el 15 a 20 por ciento de los embarazos clínicamente reconocidos. El impacto emocional se acentúa debido a la falta de diagnóstico. OBJETIVO: Describir la experiencia del Laboratorio de Citogenética de la Clínica Sanatorio Alemán de Concepción e identificarlas alteraciones más frecuentes y su relación estadística con la edad materna. MATERIAL Y MÉTODO: 677 muestras de tejido obtenidas de abortos espontáneos, ocurridos desde julio de1996 a abril de 2009. Es un trabajo de tipo transversal donde las muestras utilizadas son las vellosidades coriónicas, cultivadas en medios estandarizados. RESULTADOS: De las 677 muestras estudiadas, en 259 se obtuvo un cariotipo normal (38,3 por ciento). En 418 muestras se encontraron anomalías cromosómicas, correspondiendo estas a un 61,7 por ciento. Entre los cariogramas alterados se encontraron: 265 trisomías (63,4 por ciento), 83 poliploidías (19,9 por ciento), 48 monosomías (11,5 por ciento) y 22 alteraciones estructurales (5,3 por ciento). La trisomía más frecuente fue la 16 (34,4 por ciento), seguida de la trisomía 21 (13,6 por ciento). Se encontró una relación estadísticamente significativa entre la edad de la madre (> 37 años) y la presencia de alteraciones citogenéticas (p<0,0001). DISCUSIÓN: El 61,7 por ciento de los abortos presentó alguna alteración del cariotipo. La trisomía 16 fue la aberración más frecuente concordando con la literatura. La trisomía 21 se presentó en un 13,6 por ciento siendo más frecuente que lo encontrado en series extranjeras. En el grupo mayor de 37 años existe mayor prevalencia de anomalías cromosómicas siendo estadísticamente significativa (p<0,0001).

INTRODUCCION: The human reproduction is a relatively inefficient process. In the 15 to 20 percent of the pregnancy clinically diagnosticated finish in spontaneous abortions. The great emotional impact, that in many times is worst by the lack of diagnostic. OBJECTIVE: Describe experience of the Cytogenetic Laboratory of Clínica Sanatorio Alemán of Concepción Chile and determinate the frequency of alteration and his relationship with maternal age. MATERIAL AND METHOD: 677 samples of tissue of spontaneous abortions, taked from July, 1996 to April, 2009. It is a descriptive work; the samples are chorionic villous, cultivated in standard solutions. RESULTS: Of 677 samples in 259 was found a normal cariotype (38.3 percent). In 418 was found some type of chromosome aberrations (61.7 percent). The distribution of the abnormal result is the follow: 265 trisomies (63.4 percent), 83 polyploidy (19.8 percent), 48 monosomy (11.5 percent) and 22 abnormalities structures (5.3 percent). Of the trisomies the most recurrent is 16 trisomy with the 34.4 percent, follow by the 21 trisomy with 13.6 percent and the 22 trisomy with 12.8 percent. In the statistic analysis we found a statistically significant relation between the age of the mother (<38 years) and the development of chromosomal alterations (p<0.0001). DISCUSSION: The 61.7 percent of abortions show some cytogenetic alteration. The 16 trisomies were the most frequent, agreeing with the literature. The trisomy 21 was more common than published to date. In older women is most frequent found chromosome aberrations (p<0.0001).

The cytogenetic examination as a tool for the diagnosis of chromosomal disorders / Examinación citogenética como herramienta para el diagnóstico de los desórdenes cromosómicos

Clinically significant chromosomal abnormalities occur in about 1 percent of children born alive. The objective of this work was to offer the patients and the families in the community for the service of the Integrated Clinic of Uniara Health (Araraquara and region), the examination of cariotype (cytogenetic study) for confirmation or exclusion of the diagnostic suspicion of chromosomal abnormalities as well as information (genetic counseling) for the prevention of occurrence and/or recurrence of these anomalies. In the period of one year and four months these were carried out in the Integrated Clinic of Uniara Health and directed for the Laboratory of Cytogenetic Human of the same institution in 66 cytogenetic studies. In 44 patients (66.6 percent) the results were normal. In 22 (33.3 percent) examinations, alterations were found, meaning that the respective clinical pictures are decurrent of chromosomic alterations. The first cause within alterations noted was Down syndrome with a total of 15 examinations or 68.1 percent, the second cause of chromosomal anomaly was the Turner syndrome where the most important factor is 45, X, where 2 karyotypes of this type or 9.1 percent were found, syndromes as (Eduards syndrome, Patau syndrome, 3p- syndrome, 4p- syndrome and 6p-syndrome) diagnosed in our laboratory appeared less frequently corresponding to 22.7 percent of the studied anomalies. The work carried out constitutes a necessary diagnosis of the main chromosomal abnormalities through a low cost technique; it can be carried out easily and is reliable, making the cytogenetic examination available to the community and contributing significantly to the quality of life of patients.

Las anormalidades cromosómicas, clínicamente significativas, se presentan en aproximadamente 1 por ciento de los niños nacidos vivos. Este trabajo tiene el objetivo de ofrecer a los pacientes y /o a sus familiares el servicio de la Clínica Integrada de la Salud de Uniara (Araraquara y Región), el examen de cariotipo (estudio citogenético) para la confirmación o la exclusión de sospecha de anomalías cromosomales diagnosticadas, así como otorgar información (consejo genético) para la prevención de las posibles anomalías y /o la repetición de éstas. En un año y cuatro meses fueron realizados 66 estudios de citogenética en la Clínica Integrada de Uniara, dirigida por el Laboratorio de Citogenética Humana de la misma institución. En 44 pacientes (66,6 por ciento) los resultados fueron normales. En 22 (33,3 por ciento) de los exámenes, se encontraron alteraciones, compatibles con alteraciones cromosómicas. La primera causa de anomalías cromosómica fue el síndrome de Down, totalizando 15 exámenes (68,1 por ciento), la segunda causa fue el síndrome de Turner, con dos cariotipos (9,1 por ciento) en la forma más importante 45, X. Por otra parte, se encontró que los síndromes de Eduards, de Patau, 3p-síndrome de Down, síndrome 4p-6p, diagnosticados en nuestro laboratorio, presentaban baja frecuencia de aparición, representando el 22,7 por ciento de las anomalías estudiadas. Este trabajo permitió realizar un diagnóstico preciso de las anomalías cromosomales, principalmente a través de una técnica de bajo costo, fácil ejecución y buena confiabilidad, técnicas que están disponibles para el examen citogenético para la comunidad y así contribuir de manera significativa en la calidad de vida de los pacientes.

Arteria umbilical única y malformaciones asociadas en una serie de 5500 autopsias: implicancia en conductas perinatales / Single umbilical artery and associated malformations in a series of 5500 autopsies: implication in perinatal conducts

Con una incidencia del 1% de nacimientos, la arteria umbilical única (AUU) es, de todos los defectos congénitos, el más frecuente. Se asocia reconocidamente a una variedad de malformaciones pero existen controversias acerca de su condición de predictora de un resultado perinatal adverso y de constituir una indicación para descartar otras malformaciones. Objetivos: establecer las frecuencias de malformaciones asociadas a AUU, determinar si existen asociaciones preferenciales y cuantificar el riesgo de otras malformaciones en presencia de AUU en una serie de autopsias perinatales. Material y métodos: en 5.539 autopsias del Hospital Materno Infantil Ramón Sardá y del Laboratorio Privado de Patología Perinatal se calculó la frecuencia de cada malformación (agrupadas por aparato) asociada a la AUU y los riesgos de malformaciones asociadas. Se estableció el riesgo para anomalías cromosómicas en casos con AUU sin otras malformaciones asociadas. Resultados: la AUU fue 10 veces más frecuente en presencia de otras malformaciones. El riesgo para malformaciones se incrementó significativamente entre tres y nueve veces en presencia de AUU. Las anomalías renales y digestivas mostraron una asociación preferencial con la AUU. En ausencia de otras malformaciones agregadas, la AUU presentó un bajo riesgo para anomalías cromosómicas. Conclusiones: el diagnóstico de AUU es indicación para realizar un exhaustivo monitoreo fetal y para descartar anomalías renales y cardiovasculares. No sería indicación para realizar un estudio cromosómico fetal si no se detectan otras malformaciones.

With a birth prevalence rate of about 1%, single umbilical artery (SUA) is the most frequent congenital anomaly. It recognizably associates with a variety of birth defects but its ability to predict an adverse perinatal outcome is unclear, as well as if other malformations should be ruled out when a SUA is diagnosed. Aims: to estimate the association between SUA and other birth defects in a series of perinatal autopsies, to establish if preferential associations between SUA and certain birth defects exist, and to quantify the risks for other birth defects when a SUA is diagnosed. Material and methods: in a series of 5.539 perinatal autopsies, from the Hospital Materno Infantil Ramón Sardá and the Private Laboratory of Perinatal Pathology, Buenos Aires, the rate of each malformation (grouped by organ/system) associated with SUA and the risks of associated malformations were estimated. Results: the rate of SUA showed a 10-fold increase when other malformations were present. The risk for other malformations increased significantly, from 3 to 9-fold, when a SUA was present. Urinary and gut anomalies showed a preferential association with SUA. The absence of other birth defects lowered the risk of SUA for chromosome anomalies in almost 60 per cent. Conclusions: prenatal diagnosis of SUA should lead to an exhaustive fetal monitoring, and urinary and cardiovascular defects should be ruled out. The diagnosis of a SUA is not an indication for a fetal chromosome analysis, if no other malformations are present.

Análise citogenética em material de abortamento espontâneo / Cytogenetic analysis of material from spontaneous abortion

OBJETIVO: Descrever as anormalidades cromossômicas em material de abortamento espontâneo. MÉTODOS: Realizou-se compilação retrospectiva da análise de cariótipo em lâmina corada com Banda G por microscopia óptica e em material de 428 produtos de abortamento encaminhados para estudo. RESULTADOS: Foram observados 145 resultados normais (33,9 por cento) e 237 resultados anormais (55,4 por cento). Em 46 amostras não houve crescimento celular (10,7 por cento). As anormalidades numéricas foram as mais frequentes, destacando-se a trissomia do 16 (41 casos), a triplodia (27 casos), a monossomia do X (26 casos), a tetraploidia (13 casos) e a trissomia do 15 (13 casos). CONCLUSÃO: As alterações citogenéticas representam importante causa de perdas gestacionais e sua detecção auxilia o aconselhamento genético do casal. A trissomia do cromossomo 16 é a alteração mais frequentemente encontrada.

OBJECTIVE: To describe chromosomal abnormalities in spontaneous abortion material. METHODS: A retrospective compilation of karyotype analysis of slides stained with Band G was carried out by optical microscopy with materials of 428 abortion products referred for study. RESULTS: There were 145 normal results (33.9 percent) and 237 abnormal results (55.4 percent). In 46 samples there was no cell growth (10.7 percent). Numerical abnormalities were the most frequent, especially trisomy 16 (41 cases), triplodia (27 cases), monosomy X (26 cases), tetraploidy (13 cases) and trisomy 15 (13 cases). CONCLUSION: Cytogenetic alterations are an important cause of pregnancy loss and their detection helps the genetic counseling to the couple. Trisomy 16 is the most often found change.

Estudo citogenético de abortos espontâneos / Cytogenetical study on miscarriages

Os abortamentos espontâneos ocorrem por diversas causas, sendo as anomalias cromossômicas do concepto,as mais freqüentes. Assim, o estudo citogenético de seus produtos e genitores, seguido do aconselhamentogenético aos casais participantes, são condutas essenciais. O presente estudo retrospectivo teve comoobjetivo investigar os cariótipos de 574 amostras de produtos de abortamentos espontâneos, bem comosangue periférico de casais com abortamentos espontâneos recorrentes, para estimar a frequência de alteraçõescromossômicas. Os cariótipos foram previamente realizados a partir da cultura de vilosidade coriônica (abortos)e sangue periférico (casais), seguida da técnica de bandeamento G. Concluiu-se que as frequências observadasde alterações cromossômicas entre os abortos (19,69%) e os casais (7,6%) foram concordantes com a literatura,reforçando a importância da análise citogenética nesses casos.

Miscarriages result of several causes, but chromosomal anomalies are the most frequent. Thus, the cytogeneticstudies of its products and of the parents, followed by genetic counseling to involved couples, are crucialconducts. The present retrospective work aimed to investigate the karyotypes of 574 samples of miscarriageproducts, and the peripheral blood of couples involved with recurrent miscarriages in an attempt to estimatethe frequencies of chromosomal alterations. Karyotypes were previously made from the culture of chorionicvilli (miscarriages) and peripheral blood (couples), followed by the technique of G banding. It was concludedthat the observed frequency of abnormal karyotypes among miscarriage products (19.69%) and couples(7.6%) were both consistent with the literature, reinforcing the importance of cytogenetic study in thesecases.

Freqüência das anormalidades cromossômicas: importância para o diagnóstico citogenético / Frequency of chromosomal abnormalities: the significance for cytogenetic diagnosis

As anomalias cromossômicas fazem parte de uma das maiores categorias de doenças genéticas, sendoresponsáveis por diversas malformações congênitas e parte dos insucessos reprodutivos. Este estudo retrospectivo teve como principal objetivo analisar a freqüência de anomalias cromossômicas em 1171indivíduos, encaminhados para exame citogenético, no período de janeiro de 1998 a dezembro de 2007, aoAmbulatório e Laboratório de Genética da Unesp – Bauru. Os cariótipos foram previamente realizados com atécnica de bandeamento G em células obtidas a partir de cultura de linfócitos de sangue periférico. Os resultados mostraram 142 casos de cariótipos anormais, sendo as aneuploidias (45,1%) as mais freqüentes,seguidas pelas alterações estruturais (38,7%) e mosaicismos (16,2%). Concluiu-se que esses resultadosconcordam com a literatura pertinente, sendo de alta relevância o estudo citogenético tanto para diagnósticoem indivíduos malformados ou inférteis, como para esclarecer a etiologia da perda fetal e, assim, alertar à possibilidade de futuras malformações congênitas.

Chromosomal abnormalities are part of a larger category of genetic diseases, and responsible for various congenital malformations and part of the reproductive failures. The mainly objective of this retrospective work was to analyze the frequency of chromosomal abnormalities among 1,171 individuals referred to the Ambulatório e Laboratório de Genética, Unesp-Bauru for cytogenetic examination, from January, 1998 to December, 2007. The G-banding technique was previously used to prepare karyotypes of cells from lymphocyte culture of peripheral blood. The results showed 142 cases of abnormal karyotypes. The most frequent were aneuploidies (45.1%), followed by structural anomalies (38.7%), and mosaicisms (16.2%). It was concluded that these results are consistent with those in the literature, and they are important both for the cytogenetic diagnosis in malformed or infertile individuals, and also to clarify the etiology of fetal loss, and thus alert to the possibility of further congenital malformations.

Anomalias e prognóstico fetal associados à translucência nucal aumentada e cariótipo anormal / Fetal abnormalities and prognosis associated with increased nuchal translucency and abnormal karyotype

OBJETIVO: Descrever a frequência de anomalias cromossômicas em fetos com translucência nucal (TN) aumentada, e a frequência de malformações estruturais, a evolução e o resultado da gestação nos fetos com TN aumentada e cariótipo anormal. MÉTODOS: Estudo retrospectivo envolvendo 246 casos com medida da TN acima do percentil 95º para a idade gestacional, com cariótipo fetal conhecido ou avaliação clínica das crianças no período pós-natal. Os casos foram acompanhados no setor de Medicina Fetal do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. RESULTADOS: O resultado do cariótipo fetal esteve alterado em 14,2 por cento dos casos. O acompanhamento dessas gestações revelou anormalidade estruturais em 80,8 por cento dos fetos, sendo as anormalidades cardíacas as mais comuns (61,5 por cento). Resultados gestacionais adversos, como abortamento, óbitos intraútero e neonatal ocorreram em 76,5 por cento dos fetos. CONCLUSÃO: Translucência nucal aumentada, entre 11 - 13 semanas e 6 dias, é importante marcador de anomalias cromossômicas fetais e malformações estruturais fetais, principalmente cardíacas. Diante deste achado, há aumento do risco de abortamento, óbito intrauterino e neonatal para estas gestações.

OBJECTIVES: This study aimed to evaluate the incidence of chromosomal abnormalities in fetuses with increased nuchal translucency (NT) measurement. Incidence of structural abnormalities and pregnancy outcome was also described in fetuses with increased NT and abnormal karyotype. METHODS: This was a retrospective study involving 246 fetuses with increased NT and known karyotype followed at the Fetal Medicine Unit, Hospital das Clínicas, São Paulo University Medical School. RESULTS: Fetal karyotype was abnormal in 14.2 percent of the cases. Ultrasound anomaly scan and specialized echocardiographic studies in these cases showed fetal structural abnormalities in 80.8 percent and cardiac defects were found in 61.5 percent of the fetuses. Pregnancy outcome was abnormal in 76.5 percent of these women. CONCLUSION: Increased NT measurement at 11 to 13 weeks and 6 days is an important marker for fetal chromosomal and structural abnormalities, mainly fetal cardiac defects. This finding also indicates increased risk of spontaneous fetal and neonatal death.

Diagnóstico citogenético prenatal: experiencia de 10 años en el Hospital Regional Rancagua / Prenatal diagnosis and cytogenetics: 10 year experience in a regional hospital

Objective: To present a 10-year experience with prenatal karyiotyping in cases of fetal malformations in a Regional NHS hospital. Methods: Pregnancies complicated with congenital abnormalities detected prenatally by ultrasonography and undergoing an invasive procedure for fetal Karyotyping were reviewed. Information on maternal demographics, number and type of procedure, indications, complications, and cytogenetic results was obtained by reviewing the ultrasound reports and medical records. Results: In the 10- year period from January 1997 to December 2006, 1.139 pregnancies complicated by a fetal structural anomaly were evaluated in our unit. In 270 cases, an invasive procedure for fetal karyotyping was carried out, including 212 (78 percent) fetal blood sampling procedures, 43 (16 percent) amniocenteses, 8 ( 3 percent) chronic villus sampling procedures. In 178 (66 percent) the karyotype result was reported as normal, in 68 (25 percent) as abnormal, in 22 (8 percent) there was a culture failure, and in 2 (1 percent) a failed procedure. Among the 68 chromosomal abnormalities, 32 percent were trisomy 21 (n=22), 32 percent trisomy 18 (n=22), and 25 percent a monosomy X(n=17). In the remaining cases there was a trisomy 13, trisomy 14, triploidy, or a chromosomal structural defect. In the first 4 years, the detection rate of a chromosomal defect was approximately 15 percent, which increased to 35 percent in the last 6 years, without a significant increase in the number of procedures. Conclusions: Our unit deals with more than 100 cases of fetal malformations per year. The implementation of a cytogenetic laboratory allows the provision of critical information for the subsequent management of the pregnancy and future genetic counseling. Overall, 25 percent of the procedures yielded an abnormal result. With increasing experience, the efficiency is improving considerable without a concomitant increase in the number of procedures.

Objetivo: Presentar la experiencia acumulada de 10 años con el diagnóstico citogenético prenatal en fetos con malformaciones congénitas detectados por ultrasonografía en un hospital base del sector público. Métodos : Se revisó nuestra base de datos seleccionando aquellas pacientes evaluadas exclusivamente por malformaciones fetales únicas o múltiples que fueron sometidas a estudio citogenético prenatal. Se recolectó la información demográfica y clínica, evaluando el número total de procedimientos por año, la relación normales/anormales, el rendimiento por tipo de muestra, el porcentaje de procedimientos frustros en la toma de muestra y la fallas del cultivo. Resultados: En el período entre enero de 1997 y diciembre del 2006, se evaluaron 1.139 embarazos complicados con malformaciones congénitas, en los cuales se realizaron 270 procedimientos invasivos prenatales. De ellos 212 (78 por ciento) fueron cordocentesis, 43 (16 por ciento) amniocentesis, 8 (3 por ciento) biopsias placentarias y 7 (3 por ciento) biopsia de vellosidades coriales. En 178 (66 por ciento) casos el cariograma fue informado como normal en 68 (25 por ciento) como anormal, en 22 (8 por ciento) no hubo crecimiento de cultivo celular y en 2 (1 por ciento) hubo una punción frustra. De los 68 resultados anormales, un 32 por ciento corresponden a trisomías 21 (n=22), un 32 por ciento a trisomías 18 (n= 22) y un 25 por ciento a monosomía del cromosoma X (n=17). El 10 por ciento restante corresponde a anomalías del cromosoma 13 ó 14, triploidías o defectos estructurales rearreglos cromosómicos. De un promedio de resultados anormales de un 15 por ciento en los primeros 4 años del estudio, se mejoró la detección a un 35 por ciento en los últimos 6 años, sin un aumento significativo en el número de procedimientos. Conclusiones: Nuestra Unidad de Ultrasonografía maneja un volumen superior a los 100 casos de anomalías fetales anuales...

Cardiopatías congénitas con diagnóstico prenatal: seguimiento / Congenital heart disease with prenatal diagnosis: follow-up

Objetivo: Seguimiento de las cardiopatías congénitas con diagnóstico prenatal. Método: Se analizan todas las cardiopatías con diagnóstico prenatal que ingresaron al Centro de Referencia Perinatal Oriente (CERPO) entre Abril 2003 y Junio 2005. Se realiza seguimiento postnatal y se compara el pronóstico con la experiencia previamente reportada en la literatura. Resultados: Se detectaron 94 cardiopatías congénitas de las cuales 76,6 por ciento correspondían a pacientes referidas desde otras regiones del país. La edad gestacional promedio al diagnóstico fue de 32 semanas. La principal causa de derivación correspondió a sospecha en examen obstétrico ultrasonográfico de rutina (72 por ciento de los casos). En esta serie se detectaron 10 anomalías cromosómicas y 14 casos presentaron malformaciones extracardíacas asociadas. Los diagnósticos más frecuentes correspondieron a síndrome hipoplasia ventricular izquierdo y ventrículo único, cardiopatías de difícil tratamiento y elevada mortalidad. La sobrevida global alcanzó un 46,1 por ciento, cifra similar a estudios internacionales previamente reportados. La sobrevida fue mejor en pacientes con malformaciones cardíacas únicas, que en pacientes que presentaron malformaciones más severas. Conclusión: Es importante mejorar el diagnóstico de cardiopatías ductus dependientes aisladas para mejorar la sobrevida en estos grupos de pacientes.

Chromosomal studies in infertile men with oligozoospermia & non-obstructive azoospermia.

BACKGROUND & OBJECTIVE: Chromosomal anomalies have been postulated to be as one of the principal genetic factors in male infertility. Cytogenetic evaluation of men with severely compromised semen parameters reveals an increased incidence of chromosomal aberrations when compared with the normal population. The objective of this study was to determine the chromosomal constitution and sperm characteristics among Indian males with severe male factor infertility. METHODS: In this prospective study we investigated 88 infertile men (42 men with azoospermia and 46 men with sperm count <5 x 10(6) million/ml) prior to intracytoplasmic sperm injection (ICSI) treatment. Karyoptying was performed on peripheral blood lymphocytes according to standard methods. Polymerase chain reaction (PCR) was performed to screen the microdeletions in the AZF region of the Y chromosome. RESULTS: Constitutional chromosome abnormalities were identified in 14.3 per cent of azoospermic and 6.5 per cent of oligozoospermic men, with an overall rate of 10.2 per cent. Chromosomal abnormalities included gonosomal aberrations in 5 cases. Robertsonian translocation in one, trisomy 7 mosaicism in one case, deletion in chromosome 16 in one, and a marker chromosome in one case. Chromosome variants were observed in 33 (37.5%) subjects. Yqh- was the most frequent variant in sex chromosomes and increased length in heterochromatin and satellites were observed in autosomal chromosomes. INTERPRETATION & CONCLUSION: The high rate of chromosomal anomalies among infertile men strongly suggests the need for routine cytogenetic analysis prior to employment of assisted reproduction techniques. In addition, meticulous follow-up of babies born after ICSI, especially male offsprings, is necessary.

National Congenital Anomalies Register in the United Arab Emirates

The National Congenital Anomalies Register is a population-based register covering all births in the United Arab Emirates. We evaluated the progress of the register and determined the prevalence of congenital anomalies [CAs] and associated maternal and neonatal risk factors. Total prevalence of CAs for 1999-2001 was 7.89/1000, 10.95/1000 and 7.92/1000 for live births, stillbirths and total births respectively. Rates were comparable to international rates for all districts except Dubai, Fujairah and Ras Al Khaimah. According to the International classification of diseases, the cardiovascular system was the most affected followed by CAs of chromosomal and the musculo-skeletal system. Birth defects were more common with older maternal age, gr and multiparity, male babies, low-birth-weight babies and premature babies

Profile of major congenital malformations in neonates in Al-Jahra region of Kuwait

We investigated major congenital abnormalities in babies born in Al Jahra Hospital, Kuwait from January 2000 to December 2001. Of 7739 live and still births born over this period, 97 babies had major congenital malformations [12.5/1000 births]: 49 [50.6%] babies had multiple system malformations, while 48 [49.4%] had single system anomalies. Of the 49 babies with multiple malformations, 21 [42.8%] had recognized syndromes, most of which were autosomal recessive and 17 had chromosomal aberrations. Isolated systems anomalies included central nervous system [12 cases], cardiovascular system [9 cases], skeletal system [7 cases] and gastrointestinal system [6 cases]. Of the parents, 68% were consanguineous. Genetic factors were implicated in 79% of cases. Genetic services need to be provided as an effective means for the prevention of these disorders

Relationship Between the Extent of Chromosomal Losses and the Pattern of CpG Methylation in Gastric Carcinomas

The extent of unilateral chromosomal losses and the presence of microsatellite instability (MSI) have been classified into high-risk (high- and baseline-level loss) and low-risk (low-level loss and MSI) stem-line genotypes in gastric carcinomas. A unilateral genome-dosage reduction might stimulate compensation mechanism, which maintains the genomic dosage via CpG hypomethylation. A total of 120 tumor sites from 40 gastric carcinomas were examined by chromosomal loss analysis using 40 microsatellite markers on 8 chromosomes and methylation analysis in the 13 CpG (island/non-island) regions near the 10 genes using the bisulfite-modified DNAs. The high-level-loss tumor (four or more losses) showed a tendency toward unmethylation in the Maspin, CAGE, MAGE-A2 and RABGEF1 genes, and the other microsatellite-genotype (three or fewer losses and MSI) toward methylation in the p16, hMLH1, RASSF1A, and Cyclin D2 genes (p<0.05). The non-island CpGs of the p16 and hMLH1 genes were hypomethylated in the high-level-loss and hypermethylated in the non-high-level-loss sites (p<0.05). Consequently, hypomethylation changes were related to a high-level loss, whereas the hypermethylation changes were accompanied by a baseline-level loss, a low-level loss, or a MSI. This indicates that hypomethylation compensates the chromosomal losses in the process of tumor progression.

Prevalencia al nacimiento de aberraciones cromosómicas en el Hospital Clínico de la Universidad de Chile. Período 1990-2001 / Prevalence of chromosomal aberrations at birth in the Clinical Hospital of Universidad de Chile, 1990-2001

BACKGROUND: A cytogenetical study should be performed to every newborn with malformations. If a chromosomal aberration is found, parents must be studied to give an adequate genetic advise. AIM: To study the frequency of chromosomal aberrations in newborns with malformations. PATIENTS AND METHODS: In the Clinical Hospital of the University of Chile all malformations in newborns are registered, as part of the Collaborative Latin American Study of Congenital Malformations (ECLAMC). The frequency of chromosomal aberrations, determined by cytogenetical studies, was determined in newborns with malformations. RESULTS: In the study period, there were 32,214 births. Of these, 2,268 live newborns and 43 stillbirths had malformations. Ninety nine children with malformations had chromosomal aberrations (4.3 per cent). Trisomy 21 was the most common aberration with a rate of 23/10,000 births, followed by trisomy 18 with a rate of 4/10,000 and trisomy 18 with a rate of 1.2/10,000. Ninety four percent of these children were born alive and 16.1 per cent died before discharge from the hospital. The masculinity indexes for Down syndrome and for trisomy 18 were 0.38 and 0.61 respectively. CONCLUSIONS: A higher frequency of female gender for trisomy 21 and male gender for trisomy 18 has not been reported previously.