Reporte de caso: síndrome de Schaaf Yang / Case report: Schaag Yang síndrome

RESUMEN Introducción: El síndrome Schaaf Yang (SHFYNG) constituye un desorden multisistémico caracterizado por un grupo de signos y síntomas relacionados con alteraciones genéticas, congénitas y de expresión clínica multivariable. Fue descrito por primera vez por el Dr. Schaaf y la Dra. Yaping, profesores de Genética Molecular y Humana de la Universidad de Houston y Baylor, respectivamente, en 2013 (1). El síndrome SHFYNG tiene una herencia autosómica dominante con una mutación presente en el alelo paterno, ya que el gen MA-GEL2 tiene una impronta materna y solo se expresa el alelo paterno. A diferencia de otras patologías autosómicas dominantes clásicas, el síndrome SHFYNG puede saltar varias generaciones siempre que la mutación resida en el cromosoma materno. Presentación del caso. Preescolar femenina, con antecedente de estancia en UCIN por hipotonía neonatal y pobre succión, bronquitis y neumonía. Su fenotipo está caracterizado por facies hipotónicas, frente prominente, epicanto interno, pómulos prominentes, puente nasal bajo, nariz ancha, labio superior delgado, orejas aladas, cuello corto y obesidad central. Presenta retraso en el neurodesarrollo, lenguaje y psicomotor. Estudios genéticos: cariotipo 46,XX e hibridación genómica comparativa con patrón genómico normal, sexo femenino, en exoma trío se identifica una variante patogénica: c.1996dupC (p.Gln666Profs*47) en el gen MAGEL2 asociada con SHFYNG. Conclusión. Se informa el primer reporte de este síndrome a nivel nacional con una incidencia mundial muy baja, estimándose aproximadamente <1/1.000.000 de nacidos vivos, lo que permite ampliar el conocimiento y sospechar patologías de difícil diagnóstico como esta.

ABSTRACT Introduction: Schaaf Yang Syndrome (SHFYNG) is a multisystemic disorder characterized by a group of signs and symptoms related to genetic, congenital, and multivariate clinical alterations. It was first described by Dr. Schaaf and Dr. Yaping, professors of Molecular and Human Genetics at the University of Houston and Baylor, respectively, in 2013 (1). SHFYNG has an autosomal dominant inheritance with a mutation located in the paternal allele, since the MAGEL2 gene has a maternal imprint and only the paternal allele is expressed. Unlike other classic autosomal dominant pathologies, SHFYNG syndrome can skip several generations, as long as the mutation resides on the maternal chromosome. Presentation of the case: Female preschooler, with a history of stay in the Neonatal Intensive Care Unit, due to neonatal hypotonia and poor suction, bronchitis, and pneumonia. Her phenotype is distinguished by hypotonic facies, prominent forehead, internal epican-thus, prominent cheekbones, low nasal bridge, broad nose, thin upper lip, winged ears, short neck, and central obesity. She presents neurodevelopmental, language, and psychomotor delay. Genetic studies: 46,XX karyotype, comparative genomic hybridization: normal genomic pattern, female sex, trio exam a pathogenic variant c.1996dupC (p.Gln666Profs*47) in the MAGEL2 gene associated with SHFYNG syndrome. Conclusion: It is reported to be the first national report of this syndrome, with a very low worldwide incidence, estimating approximately <1 / 1,000,000 live births, which allows us to expand knowledge and suspect difficult-to-diagnose pathologies like this one.

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)

Trombocitopenia hereditaria relacionada a gen MYH-9: primera familia reportada en Chile con diagnóstico molecular: caso clínico / Hereditary thrombocytopenia associated with a mutation in the MYH-9 gene: report of one case

We report a 51-year-old female who had a first episode of thrombocytopenia at 23 years of age during a pregnancy. At the age of fifty, a hysterectomy was indicated due to a metrorrhagia: a platelet count of 21,000/ul was detected. She was treated with eltrombopag with a good response. The family history of the patient revealed the presence of thrombocytopenia in several family members. Suspecting a hereditary thrombocytopenia, a genetic study revealed a mutation in the MYH-9 gene. This mutation can be suspected when there is a family history of thrombocytopenia with autosomal dominant inheritance, macrothrombocytopenia and in this particular case, due to the response to thrombopoietin receptor agonist, eltrombopag.

Informed Consent Template and Guidelines on the Ethical Practice in Human Genetics and Human Genomic Research; Initiatives of the Universiti Sains Malaysia

Malaysia is advancing and nearly on pace with the international scientific community in human genetics and human genomics research. However, this research poses unique challenges. Although Malaysia already regulates medical genetic services, these regulations are insufficient for coping with the ethical issues emerging from recent genomic technologies. The Universiti Sains Malaysia recently created in-house guidelines and an informed consent template for genetic and genomic research. This article presents these guidelines and the informed consent template and discusses the justification and the background of the initiative. We also propose recommendations pertaining to local social studies and regulatory arrangements.

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.

Recollections of J.B.S. Haldane, with special reference to Human Genetics in India.

This paper is a brief account of the scientific work of J.B.S. Haldane (1892–1964), with special reference to early research in Human Genetics. Brief descriptions of Haldane's background, his important contributions to the foundations of human genetics, his move to India from Great Britain and the research carried out in Human Genetics in India under his direction are outlined. Population genetic research on Y-linkage in man, inbreeding, color blindness and other aspects are described.

Array-based Comparative Genomic Hybridization and Its Application to Cancer Genomes and Human Genetics

Microarray comparative genomic hybridization (CGH) has proven to be a specific, sensitive, and rapid technique, with considerable advantages compared to other methods used for analysis of DNA copy number changes. Array CGH allows for the mapping of genomic copy number alterations at the sub-microspecific level, thereby directly linking disease phenotypes to gene dosage alterations. The whole human genome can be scanned for deletions and duplications at over 30,000 loci simultaneously by array CGH (~40 kb resolution). Array CGH can be used for analysis of DNA copy number aberrations that cause not only cancer and human genetic disease, but also normal human variation. This review gives the various array CGH platforms and their applications in cancer and human genetics.

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.

Is the Central Valley of Costa Rica a genetic isolate?: [review]

In the last decade, the Costa Rican Central Valley population (CRCV), has received considerable scientific attention, attributed in part to a particularly interesting population structure. Two different and contradictory explanations have emerged: (1) An European-Amerindian-African admixed population, with some regional genetic heterocigosity and moderate degrees of consanguinity, similar to other Latin-American populations. (2) A genetic isolate, with a recent founder effect of European origin, genetically homogeneous, with a high intermarriage rate, and with a high degree of consanguinity. Extensive civil and religious documentation, since the settlement of the current population, allows wide genealogy and isonymy studies useful in the analysis of both hypotheses. This paper reviews temporal and spatial aspects of endogamy and consanguinity in the CRCV as a key to understand population history. The average inbreeding coefficients (a) between 1860 and 1969 show a general decrease within time. The consanguinity in the CRCV population is not homogeneous, and it is related to a variable geographic pattern. Results indicate that the endogamy frequencies are high but in general it was not correlated with a values. The general tendency shows a consanguinity decrease in time, and from rural to urban communities, repeating the tendencies observed in other countries with the same degree of development, and follows the general Western World tendency. Few human areas or communities in the world can be considered true genetic isolates. As shown, during last century, the CRCV population has had consanguinity values that definitively do not match those of true genetic isolates. A clear knowledge of the Costa Rican population genetic structure is needed to explain the origin of genetic diseases and its implications to the health system.

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.