Síndrome de Wolf-Hirschhorn por translocación: a propósito de un caso

RESUMEN El síndrome de Wolf-Hirschhorn (WHS) es una enfermedad genética causada por la pérdida de una porción distal en el brazo corto del cromosoma 4 que se caracteriza porque los pacientes presentan un rasgo craneofacial típico. Se presenta el caso de una niña de 7 meses de vida con malformaciones diversas y alimentación nasogástrica, para la realización de las técnicas de Hibridación in situ fluorescente (FISH) y cariotipo. Por FISH se detectó la microdeleción del brazo corto del cromosoma 4, región p16.3 y en el cariotipo se observó una translocación desequilibrada entre el brazo corto del cromosoma 4 y una pieza extra de origen desconocido. A fin de determinar el origen de la translocación, se realizó el estudio cromosómico a los padres, con resultados normales. Este caso revela la necesidad de la realización del FISH en pacientes con múltiples malformaciones y sospecha de ser portadores de microdeleción cromosómica.

ABSTRACT Wolf-Hirschhorn syndrome (WHS) is a genetic disease caused by the loss of a distal portion in the short arm of chromosome 4. It is characterized by the fact that patients present a typical craniofacial feature. The case of a 7-month-old girl with various malformations and nasogastric feeding is presented, on whom fluorescent in situ hybridization (FISH) and karyotype techniques were performed. By FISH, the microdeletion of the short arm of chromosome 4, region p16.3, was detected and in the karyotype an unbalanced translocation was observed between the short arm of chromosome 4 and an extra piece of unknown origin. In order to determine the origin of the translocation, the chromosomal study was performed on the parents, with normal results. This case reveals the need to perform FISH in patients with multiple malformations and suspected carriers of chromosomal microdeletion.

Evaluación del curso virtual de Genética Humana en estudiantes universitarios de ciencias de la salud / Evaluation of the Human Genetics virtual course by university health sciences students

Introducción: Los entornos de aprendizaje en línea ofrecen nuevas formas de comunicación que permiten a docentes y estudiantes intercambiar información, conocimientos e ideas, tanto en espacios asincrónicos como en tiempo real. En esta modalidad se desarrolló un curso electivo de Genética Humana para complementar la formación de estudiantes de pregrado del área de la salud. Objetivo: Evaluar la satisfacción con el uso y la percepción del trabajo en una asignatura virtual de Genética Humana en estudiantes universitarios pertenecientes a carreras del área de la salud de la Universidad de Concepción. Métodos: Estudio de tipo cuantitativo, no experimental y transversal. Mediante una encuesta de preguntas cerradas y abiertas, se determinó el grado de satisfacción de los estudiantes con respecto a los aspectos pedagógicos, tecnológicos y el ambiente virtual de aprendizaje. Resultados: Los estudiantes evaluaron en forma satisfactoria el curso virtual. En cuanto a la percepción del ambiente virtual, las opiniones positivas estuvieron centradas en la autonomía (40 por ciento) y en la experiencia de aprendizaje (38 por ciento). Los aspectos negativos se enfocaron en la responsabilidad hacia el aprendizaje (75 por ciento) y la relación con el docente (25 por ciento). Conclusiones: El curso virtual es útil para el aprendizaje de la Genética Humana, y constituye un espacio que favorece la adquisición de conocimientos y el desarrollo de competencias como la autonomía y el trabajo en equipo(AU)

Introduction: Online learning environments offer new forms of communication allowing teachers and students to exchange information, knowledge and ideas, either asynchronously or in real time. An elective Human Genetics course was taught online to complement the training of undergraduate health sciences students. Objective: Evaluate the satisfaction with and perception of the work done in a virtual Human Genetics course taught to university health sciences students from the University of Concepción. Methods: A quantitative cross-sectional non-experimental study was conducted. A survey containing open-ended and closed-ended questions was used to determine the students' level of satisfaction with pedagogical and technological aspects of the course, and with the virtual learning environment. Results: Students ranked the virtual course as satisfactory. Concerning perception of the virtual environment, positive opinions referred to the students' autonomy (40 percent) and the learning experience itself (38 percent). Negative opinions focused on the students' responsibility towards learning (75 percent) and their relationship to the teacher (25 percent). Conclusions: The virtual course proved to be useful to learn about Human Genetics, as well as an environment fostering the acquisition of knowledge and the development of competences such as autonomy and team work(AU)

Interacciones génicas implicadas en la aparición anticipada de cáncer de mama invasor en la población "paisa" - Colombia / Gene interaction implicated in genetic anticipation of invasive breast cancer in a "paisa" population - Colombia

Resumen El cáncer de mama invasor es una neoplasia de origen multifactorial en el cual están involucrados tanto componentes genéticos, como no genéticos, los cuales pueden modular su aparición temprana. El objetivo de este estudio es evaluar la participación de los componentes genéticos. Metodología: se analizaron 165 mujeres con cáncer de mama pertenecientes a la población "paisa" y estratificadas por edad de diagnóstico. Se evaluaron variables no genéticas y, de forma indirecta, variables genéticas usando marcadores tipo short tándem repeats (STR). Resultados: no se detectaron diferencias en cuanto a los factores de riesgo no genético entre pacientes mayores y menores de 50 años, ni al evaluar los genes de forma individual. Al comparar combinaciones genéticas se detectaron dos interacciones génicas en mujeres menores de 50 años: BRCA2-BRCA1 (p= 0,04) y BRCA2-ATM (p= 0,008). Conclusión: estos resultados sugieren la participación de la interacción de dichos genes en la aparición de cáncer de mama antes de los 50 años. Dado que el estudio se hizo con marcadores indirectos es necesario realizar estudios posteriores para identificar las mutaciones funcionales que soporten estos hallazgos.

Abstract Invasive breast cancer is a multifactorial neoplasm, involving both genetic and non-genetic components that modulate their early appearance of the disease. The aim of this study was to evaluate the contribution of genetic factors and disease. Methodology: 165 breast cancer patients stratified by age and belonging to the "paisa" population participated in the study. No genetic variables were controlled, and genetic variables were indirectly evaluated using short tandem repeats (STR) markers. Results: No differences were detected in non-genetic risk factors among patients older and younger than 50 years, not even in the individual evaluation of genes. When genetic combinations were evaluated, two interactions were detected in women younger than 50 years: BRCA2-BRCA1 (p= 0,04) and BRCA2-ATM (p= 0,008). Conclusion: These results suggest the involvement of gene interaction BRCA1-BRCA2 and BRCA2-ATM genes in the case of early onset of breast cancer (before the age of 50). Since the study was made with indirect markers, is necessary to perform further studies to identify the functional mutations that support these findings.

O processo e a prática do aconselhamento genético no Brasil: uma revisão de escopo / The process and practice of genetic counseling in Brazil: a scope review

Nessa dissertação foi realizada uma scoping review (SR) com objetivo de buscar na literatura o que existe, até o presente momento, para verificar as principais evidências científicas referentes ao processo e à prática do aconselhamento genético (AG) no Brasil. O método apresentado nessa revisão, scoping review, é utilizado para investigar conceitos-chave subjacentes a uma nova área de pesquisa, explorar de forma sistematizada os conceitos, teorias, evidências e lacunas referentes a um tema específico. O estudo propôs como questão de pesquisa: "Quais são as evidências científicas referentes ao processo e à prática do AG no Brasil?" Os descritores e palavras-chave prioritariamente utilizados para realizar a busca nas bases de dados foram: genetic counseling OR genetic service, Latin America OR South America OR Brazil OR Brazilian. Após utilizar a estratégia de busca, específica para cada uma das seis bases de dados (PubMed, EMBASE, SCOPUS e Web of Science, CINAHL e LILACS), foram encontrados 1028 artigos, os quais foram exportados para o software Rayyan QCRI e removidos aqueles que se encontravam em duplicata. Foram excluídos artigos em duplicata entre as bases supracitadas; trabalhos que se referiam a modelos animais, relatos de casos, editoriais, cartas, revisões de literatura, resumos e dissertações e teses; literatura cinzenta; e que não haviam sido produzidos no Brasil. Por meio desse software, dois revisores executaram, de forma independente, a leitura dos títulos e resumos de 609 artigos e 62 foram selecionados para a leitura na íntegra. Dentre esses últimos, apenas 25 de fato respondiam à questão de pesquisa. De acordo com os estudos que compuseram a amostra final desta revisão, percebe-se que ainda não há um consenso sobre os modelos de prática de AG utilizados no Brasil e nem clareza sobre as ações que compôem o processo de aconselhamento. O AG, marjoritariamente é realizado por médicos, embora esteja evidenciado na literatura a importância da equipe multiprofissional. Vale salientar, que se trata de uma área de estudo em ascenção, pois possui uma grande demanda e apresenta um número de publicações crescente a cada ano

In the present dissertation, the author carries out a scoping review (SR) to analyse the main scientific evidences concerning the process and the practice of Genetic Counselling (GR) in Brazil. The scoping review method is used to investigate key-concepts present in a new area of research and to explore, in a systematized way, the concepts, theories, evidences and omissions regarding a specific subject. This study proposes as its subject of research the following question: "what are the scientific evidences regarding the process and the practice of GR in Brazil?". The descriptors and key-words primarily used in the research in databases were: genetic counselling OR genetic service, Latin America OR South America OR Brazil OR Brazilian. Research strategies tailored to each one of the six databases (PubMed, EMBASE, SCOPUS, y Web of Science, CINAHL y LILACS) led to 1028 articles, which were exported to the Rayyan QCRI software. Articles that were published in more than on database, works regarding animal models, case reports, editorials, letters, literature reviews, summaries, dissertations, theses, grey literature, and works that were not published in Brazil were all excluded. Making use of this software, two independent reviewers read the titles and summaries of 609 articles, from among which 62 were selected to be fully read. Only 25 of these 62 articles effectively answered the question proposed in the dissertation. The studies present in the final sample of this revision show that there is not a consensus regarding the models of practice of GR used in Brazil, as well as that there is a lack of clarity concerning the actions that are part of the counselling process. RG is mainly performed by doctors, in spite of the fact that the specialized literature shows the importance of multiprofessional teams. It is important to highlight the importance of this area of research, as shown by an increasing demand and by a growing number of studies published every year

Aspectos bioéticos en el ejercicio actual de la genética humana / Bioethical aspects in current human genetics

En los últimos años las ciencias de la vida y la salud han conseguido hitos importantes permitiendo el surgimiento la ingeniería genética, la genética médica y la genómica, ramas que plantean la necesidad de criterios científicos y técnicos basados en la conducta y labor de sus profesionales. Es así que consideramos importante reflexionar desde el punto de vista bioético los siguientes temas: Las pruebas de paternidad, que tienen como objeto determinar el vínculo genético ascendente en primer grado entre un individuo y su progenitor masculino. El tamiz de portadores que se utiliza para determinar si una persona es portadora de una enfermedad genética, suele aplicarse a heterocigotos para un gen recesivo, en reordenamientos cromosómicos. La eugenesia, concebida como una ideología social, como ciencia es la rama de la manipulación genética que estudia el perfeccionamiento de la especie humana. La clonación humana, ha demostrado que se puede reprogramar una célula diferenciada de un individuo adulto, convirtiendo una célula altamente especializada en un embrión y hacerla volver atrás en su programa genético, obteniendo así un ser idéntico al primero. Como profesionales de la salud preservamos la vida, sin olvidar que debemos tratar de ofrecer una adecuada calidad de la misma a nuestros pacientes y dentro de condiciones éticas.

Nowdays, the life and health sciences have achieved significant milestones allowing the emergence of new branches, such as genetic engineering, molecular genetics, medical genetics and genomics, which pose scientific and technical criteria to sort and conduct their professional work. Thus, we consider important to analyze and reflect from the bioethical standpoint advances in the field of human genetics, addressing the following topics: Paternity tests, studies that are intended to determine the genetic link up (kinship) in the first degree between an individual and his male parent. The carrier screening used to determine whether a person is a carrier of a genetic disease, usually applied to individuals heterozygous fora recessive gene, or individuals heterozygous fora dominant gene that do notexpress the disease and chromosomal rearrangements. Eugenics, conceived as a social ideology, is defined as improving a species, as a science is the branch of genetic engineering that studies the improvement of the human species. Human cloning is a topic that generates more discussion not only from an ethical view, but also philosophical and religious points of view, since it has been shown that you can reprogram a differentiated cell of an adult, becoming a highly specialized cell into an embryo and make it go back in their genetic program, thus obtaining identical to the first one. As health professionals, we try to preserve life, not forgetting that we should give adequate quality of life to our patients with ethical conditions.

História da genética no Brasil: um olhar a partir do Museu da Genética da Universidade Federal do Rio Grande do Sul / History of genetics in Brazil: a view from the Museu da Genética at the Universidade Federal do Rio Grande do Sul

Aborda o contexto de criação do Museu da Genética, em 2011 no Departamento de Genética na Universidade Federal do Rio Grande do Sul, em Porto Alegre, e apresenta sua estrutura e conteúdo. Argumenta-se que os materiais disponibilizados no Museu da Genética constituem uma rica fonte para pesquisas sobre a história da genética no Brasil (e da genética de populações humanas em particular) a partir da segunda metade do século XX, tema ainda pouco investigado, apesar da proeminência dessa área do conhecimento no Brasil.

This work addresses the context of the creation, as well as the structure and contents, of the Museum of Genetics (Museu da Genética), created in 2011 and located in the Department of Genetics of the Federal University of Rio Grande do Sul (Universidade Federal do Rio Grande do Sul), in Porto Alegre, Brazil. The materials available at the Museum of Genetics are a rich resource for research on the history of genetics in Brazil (and especially the genetics of human populations) beginning with the second half of the twentieth century. Despite the prominence of the field of genetics in Brazil, little research has been done on this topic.

Testigos modestos y poblaciones invisibles en la cobertura de la genética humana en los medios de comunicación colombianos / Modest witnesses and invisible populations in media coverage of human genetics in Colombia / Testemunhas modestas e populações invisíveis na cobertura da genética humana na mídia colombiana

En este artículo exploramos cómo los medios de comunicación colombianos configuran la práctica de la genética humana, reproduciendo ciertos discursos estandarizados sobre ciencia que se encuentran atravesados por el género y la raza. Para este fin llevamos a cabo un análisis etnográfico de la cobertura de la genética humana (poblacional y forense) en dos de los medios de mayor penetración en el país en los periodos de 1992-2006 (periódico) y 2009-2010 (periódico y noticiero). Nuestro argumento es que por una parte, los medios de comunicación presentan a la ciencia genética como única/uniforme/objetiva/neutra/heroica. Por otro lado, presenta sujetos que son simultáneamente marcados y desmarcados en términos de raza, género, clase y geografía. Concluimos que este último mecanismo reproduce y moviliza la idea del mestizaje como una ideología de construcción de nación.

In this paper we explore the ways in which mass media present -and co-produce- human genetic research in Colombia, reproducing certain standardized discourses about science which are cross-cut by gender and race. For this, we conducted an ethnographic analysis of media coverage of human genetics (both population and forensic) in two of the major media in Colombia between 1992-2006 (newspaper) and 2009-2010 (TV news). Our argument is two-fold. First we show that media present genetic science as unique/uniform/objective/neutral/heroic. Second, media present subjects as simultaneously marked and unmarked in terms of race, gender, class, and geography. We conclude by arguing that this mechanism reproduces and mobilizes the ideal of mestizaje as a nation-building ideology in Colombia.

Neste artigo apresenta-se a forma como a mídia colombiana configura a prática da genética humana por meio da reprodução de discursos padronizados de ciência que são atravessados pelo gênero e a raça. Para isso, realizamos uma análise etnográfica da cobertura da genética humana (de populações e forense) no principal jornal impresso e no maior telejornal do país nos períodos 1992-2006 (jornal) e 2009-2010 (jornal e telejornal). Nosso argumento é de que, por um lado, a mídia apresenta a ciência da genética como única/uniforme/objetiva/neutra/heróica. Do outro, apresenta sujeitos que são marcados e desmarcados em termos de raça, gênero, classe e geografia. Como conclusão, aponta-se que o último mecanismo reproduz e mobiliza a ideia da mestiçagem como uma ideologia de construção da nação.

Frecuencia de la mutación p. Q829X del gen Otoferlina (otof) en población colombiana con sordera no sindrómica / Frequency of p. Q829X Mutation in Otoferlin Gene in Colombian Population with non Syndromic Deafness

Introducción: Las pérdidas auditivas son heredables en un 50-60% de los casos. Dentro de estas, las sorderas no sindrómicas predominan y se han descrito más de 40 genes asociados. Uno de los más frecuentemente implicados es el gen de Otoferlina(OTO F). Objetivo: Determinar la frecuencia de la mutación p.Q829X en el gen OTO F en 649 individuos colombianos con sordera no sindrómica. Materiales y métodos: Se seleccionó una población de 649 individuos para realizar la búsqueda de la mutación p.Q829X por medio de la técnica PCR-RFLP. Resultados: Se identificaron 12 individuos con la mutación p.Q829X (12/649), quecorresponden a una frecuencia del 1,8%. Conclusiones: La mutación p.Q829X es la más frecuente en el gen OTO F, y la tercera luego de las mutaciones S199F y 35delG en el gen GJB2, causantes de sordera en la población analizada. Se observó variabilidad en el grado de pérdida auditiva en los individuos homocigotos para la mutación y presencia deneuropatía auditiva en el 62,5% de estos casos...

Introduction: Hearing loss is 50-60 % heritable. Among this, non-syndromic hearing loss is predominant and more than 40 genes have been reported. One of the most frequently involved is OTO F gene. Objective: To identify the frequency of mutation p.Q829X in OTO F gene, in 649 Colombian individuals with non-syndromic deafness. Materials and Methods: A total of 649 individuals were selected and screened for p.Q829X mutation using PCR-RFLP analysis. Results: p.Q829X mutation was identified in 12 deaf individuals (12/649) corresponding to a frequencyof 1,8%. Conclusions: p.Q829X mutation is the most common in OTO F gene, and the third cause after S199F and 35delG mutations in GJB2 gene, ofdeafness in the analyzed population. Variability is observed in the degree of hearing loss in individuals homozygous for the mutation and auditoryneuropathy is present in 62,5% of these cases...

Análise genética de problemas craniofaciais: revisão da literatura e diretrizes para investigações clínico-laboratoriais (parte 1) / Genetic analysis of craniofacial problems: a review of the literature and some guidelines for clinical and laboratorial investigation (part 1)

INTRODUÇÃO: cada vez mais se descobre que os genes têm papel fundamental na etiologia dos problemas craniofaciais, no entanto, o conhecimento das bases da genética humana ainda está muito distante da prática diária do cirurgião-dentista clínico. OBJETIVO: o objetivo deste trabalho é ser uma fonte de consulta, provendo o leitor com conceitos e nomenclaturas pertinentes à área da genética humana. METODOLOGIA: os autores apresentam e revisam os principais tópicos relacionados à genética investigativa, sobretudo no que diz respeito às doenças ou distúrbios multifatoriais e complexos que alteram o processo normal de crescimento e desenvolvimento craniofacial. RESULTADOS E CONCLUSÕES: é essencial que esses profissionais se atualizem para poder acompanhar os progressos atuais e futuros, tanto na área clínica investigativa quanto na área das pesquisas moleculares laboratoriais.

INTRODUCTION: New researches show the important role played by genes in the etiology of craniofacial problems. In spite of that, knowledge of the basis of Human Genetics is still very far from the daily practice of clinical dentists. AIM: The main aim of this paper is to serve as a valuable source of information on Genetics for readers, supplying them with the main concepts and nomenclature in this field. METHODS: The authors provide an overview of central concepts and topical issues in modern genetic investigation, with special attention to the complex and multifactorial disorders that disturb the normal process of craniofacial growth and development. RESULTS AND CONCLUSION: It is indispensable for updated clinical dentists to have at least a basic knowledge about the basis of Human Genetics in order to follow its current and future progresses in both areas: clinical investigative and Molecular Genetics.

Diagnóstico y tamizaje del retardo mental hereditario más común, situación en Costa Rica / I commonest diagnose and tamizaje of the hereditary mental retardation, situation in Costa Rica

El síndrome del cromosoma X frágil (FRAXA) es la segunda causa genética de retardo mental y la forma más frecuente de retardo mental hereditario. FRAXA es causante de discapacidades que van desde grados variables de problemas de aprendizaje hasta retardo mental. Con frecuencia se asocian retrasos severos en el lenguaje, problemas de conducta, comportamiento semejante al autista, testículos agrandados, orejas grandes o prominentes, hiperactividad, retraso en el desarrollo motor y deficiente integración sensorial. Se hace un resumen del conocimiento actual de esta patología y del trabajo de los autores. Se tocan temas como el producto génico, los métodos de diagnóstico, el cuadro clínico, la epidemiología, la prevención, el tratamiento, el tamizaje y la situación en Costa Rica.

Fragile X syndrome (FRAXA) is the most common type of hereditary mental retardation, and the second commonest with genetic origin. The range of affection in FRAXA includes from learning problems to mental retardation. The syndrome includes speech and language deficits, abnormal behaviours, including autistic features, macro orchidism, prominent ears, hyperactivity, sensorial integration and motor impairments. Actual data and the authors own work is reviewed. Topics approached are the gene product, diagnostic methodology, clinical picture, epidemiology, prevention, screening and the actual situation in Costa Rica regarding this pathology.

El diagnóstico prenatal de defectos cromosómicos en Costa Rica: [revisión] / Prenatal diagnosis of chromosomic defects in Costa Rica: [review]

This is an historical overview of prenatal cytogenetic diagnosis in Costa Rica. It started in 1984 at the Institute for Health Research of the University of Costa Rica. This is the only fetal cytogenetic diagnosis facility in the country and serves social security as well as private patients. Perinatologists send amniotic fluid and fetal blood samples from high risk pregnancies, mainly due to abnormal ultrasound assessment, sonographic markers of aneuploidy and advanced maternal age. Second and third trimester diagnosis allows the development of coping strategies for the families of affected fetuses, since pregnancy interruption is not permitted. Normal fetal cytogenetic results provide reassurance to the parents.

Pasado, presente y futuro de la citogenética en Costa Rica: [review] / Past, present and future of cytogenetics in Costa Rica: [review]

This is an overview of the past, present and future of human Cytogenetics in Costa Rica. It started in 1965 at the University of Costa Rica where it has been developed slowly but steadily. There is only one overloaded clinical cytogenetic laboratory in the social security system. The tests currently performed are peripheral blood and blood marrow karyotypes, prenatal cytogenetic diagnosis (amniotic fluid and fetal blood) and less frequently skin biopsies. The task now is to standardize molecular cytogenetic techniques, we are actually working with PRINS in order to study submicroscopic subtelomeric rearrangements associated with mental retardation and other microdeletion syndromes as well.

Las mutaciones inestables, nuevo reto para el consejo genético de enfermedades hereditarias: [revisión] / Unstable mutations, new challenges for genetic counseling of inherited disorders: [review]

Unstable mutations or amplification of DNA tandem repeats sequences constitute a new kind of genetic alteration discovered in the 90's that cause hereditary diseases. This mutation has been found inside or near important genes involved in the normal neurological function in human beings. In some cases, the presence of the amplification causes altered expression of the genes, their inactivation or the synthesis of a protein with new functions. Some common characteristics of these diseases are that they affect the central nervous system and are degenerative in nature. Most of them show genetic anticipation meaning that the severity of the manifestations increases in each generation and appear at an earlier age. In most cases, the severity of the symptoms is positively correlated with the size of the amplification. Twenty illnesses caused by this kind of mutations have been identified so far. Briefly, this work reviews the current knowledge about this topic.