Normas éticas para la realización de pruebas predictivas en los servicios de genética médica de Cuba / Ethical norms for the execution of predictive tests in the medical genetics´ services in Cuba

Introducción: Las nuevas tecnologías disponibles en el campo de la genética humana y médica pueden ser utilizadas, cada vez más, con fines médicos preventivos. Existe también el riesgo de su uso indebido que favorezca la discriminación y la eutanasia selectiva y minimice el papel de los condicionantes sociales en la salud de las poblaciones. Objetivo: Establecer normas éticas para garantizar que las pruebas presintomáticas en Cuba se realicen conforme a los principios éticos de respeto a la autonomía, justicia, beneficencia y no maleficencia. Métodos: Estas normas se elaboraron a partir de una propuesta discutida y consensuada en talleres nacionales con la participación de genetistas clínicos de todo el país y aprobadas por el Comité de Ética del Centro Nacional de Genética Médica y el Ministerio de Salud Pública. Resultados: Las normas aprobadas consideraron aspectos esenciales como el conocimiento sobre el alcance de la información que la prueba revelará y sus implicaciones a nivel personal y familiar, el consentimiento informado para su realización, las condiciones en que se realiza y la seguridad de sus resultados, las obligaciones médicas antes, durante y después de la realización de la prueba y lo concerniente a la privacidad y confidencialidad de la información. Conclusiones: La generalización y cumplimiento de las normas aprobadas asegura la protección a individuos y familias vulnerables, contribuye a mejorar su atención médica y a aminorar el impacto que sobre su salud, su reproducción y su vida en general, tienen las severas enfermedades para las que están en riesgo o padecen(AU)

Introduction: New technologies available in the field of human and medical genetics can increasingly be used for preventive medical purposes. There is also the risk of misuse that favors discrimination and selective euthanasia, and that minimizes the role of social determinants in the health of the populations. Objectives: To establish ethical norms to ensure that presymptomatic tests in Cuba are carried out in accordance with the principles of respect for autonomy, justice, beneficence and non-malice. Methods: These norms were elaborated from a proposal discussed and agreed upon in national workshops with the participation of clinical geneticists from all over the country and approved by the Ethics Committee of the National Center of Medical Genetics and the Ministry of Public Health. Results: The approved norms considered essential aspects such as: the knowledge about the scope of information that the test will reveal and its implications on a personal and family level, informed consent for its implementation, the conditions under which it is performed, and the safety of its results; medical obligations before, during and after the performance of the test; and all concerning to the privacy and confidentiality of the information. Conclusions: The generalization and compliance of these ethical norms ensure the protection of vulnerable individuals and families, contributes to improving their medical care and to reducing the impact on their health, their reproduction and life in general terms of the severe diseases they are at risk or suffering from(AU)

Normas éticas para la realización de pruebas predictivas en los servicios de genética médica de Cuba / Ethical norms for the execution of predictive tests in the medical genetics´ services in Cuba

Introducción: Las nuevas tecnologías disponibles en el campo de la genética humana y médica pueden ser utilizadas, cada vez más, con fines médicos preventivos. Existe también el riesgo de su uso indebido que favorezca la discriminación y la eutanasia selectiva y minimice el papel de los condicionantes sociales en la salud de las poblaciones. Objetivo: Establecer normas éticas para garantizar que las pruebas presintomáticas en Cuba se realicen conforme a los principios éticos de respeto a la autonomía, justicia, beneficencia y no maleficencia. Métodos: Estas normas se elaboraron a partir de una propuesta discutida y consensuada en talleres nacionales con la participación de genetistas clínicos de todo el país y aprobadas por el Comité de Ética del Centro Nacional de Genética Médica y el Ministerio de Salud Pública. Resultados: Las normas aprobadas consideraron aspectos esenciales como el conocimiento sobre el alcance de la información que la prueba revelará y sus implicaciones a nivel personal y familiar, el consentimiento informado para su realización, las condiciones en que se realiza y la seguridad de sus resultados, las obligaciones médicas antes, durante y después de la realización de la prueba y lo concerniente a la privacidad y confidencialidad de la información. Conclusiones: La generalización y cumplimiento de las normas aprobadas asegura la protección a individuos y familias vulnerables, contribuye a mejorar su atención médica y a aminorar el impacto que sobre su salud, su reproducción y su vida en general, tienen las severas enfermedades para las que están en riesgo o padecen(AU)

Introduction: New technologies available in the field of human and medical genetics can increasingly be used for preventive medical purposes. There is also the risk of misuse that favors discrimination and selective euthanasia, and that minimizes the role of social determinants in the health of the populations. Objectives: To establish ethical norms to ensure that presymptomatic tests in Cuba are carried out in accordance with the principles of respect for autonomy, justice, beneficence and non-malice. Methods: These norms were elaborated from a proposal discussed and agreed upon in national workshops with the participation of clinical geneticists from all over the country and approved by the Ethics Committee of the National Center of Medical Genetics and the Ministry of Public Health. Results: The approved norms considered essential aspects such as: the knowledge about the scope of information that the test will reveal and its implications on a personal and family level, informed consent for its implementation, the conditions under which it is performed, and the safety of its results; medical obligations before, during and after the performance of the test; and all concerning to the privacy and confidentiality of the information. Conclusions: The generalization and compliance of these ethical norms ensure the protection of vulnerable individuals and families, contributes to improving their medical care and to reducing the impact on their health, their reproduction and life in general terms of the severe diseases they are at risk or suffering from(AU)

Miopatias com padrão distal: descrição clínica de pacientes do Estado da Bahia / Distal myopathies: clinical description of patients from the State of Bahia

INTRODUÇÃO: As miopatias são doenças cuja etiologia decorre de alterações estruturais e/ou funcionais no músculo esquelético. As miopatias distais são doenças musculares primárias em que fraqueza e, frequentemente atrofia, tem início nas mãos, antebraços, pés e segmento distal das pernas. Apesar de terem sido divididas como um grupo restrito de doenças, outras miopatias podem se manifestar com um padrão distal, como a miopatia nemalínica e as distrofias musculares cintura-membros. Devido à escassez de trabalhos que descrevem clinicamente as miopatias distais, este trabalho visou contribuir com essa caracterização. METODOLOGIA: Os pacientes foram selecionados no ambulatório de doenças neuromusculares do Hospital Universitário Professor Edgar Santos, em seguida avaliados clinicamente, através de exame físico e também com exames complementares: eletroneuromiografia, exames laboratoriais, estudo molecular e histopatológico. RESULTADOS: Quinze pacientes com padrão distal foram analisados, sendo 40% do sexo feminino, média de idade de 29,8 anos, seis (40|%) pacientes naturais da capital, Salvador-Bahia. Quanto ao padrão de distribuição de fraqueza, sete apresentavam padrão distal, enquanto oito, padrão distal-proximal. Os pacientes foram agrupados de acordo com a idade de início dos sintomas, sendo 11 iniciados na infância e adolescência (T em homozigose), um com sarcoglicanopatia (mutação c.229C>T em homozigose) e um com miopatia nemalínica (histopatológico com presença de corpos nemalínicos). DISCUSSÃO: Os achados identificados nos pacientes com diagnósticos firmados foram compatíveis com o que é visto na literatura, como apresentação clínica e mutações identificadas previamente. Destaca-se o componente distal pronunciado da paciente com sarcoglicanopatia, considerado incomum. Além disso, a descrição da ressonância magnética realizada nos indivíduos demonstrou um padrão típico. Na maior parte dos pacientes não se chegou a um diagnóstico etiológico, a despeito da investigação realizada com os exames complementares e clínicos. CONCLUSÃO: O presente estudo caracterizou uma amostra de pacientes com miopatias distais, corroborando que essas doenças se manifestam clinicamente de forma heterogênea. A caracterização e divisão entre grupos visa tornar mais fácil a investigação, devendo ser feita com exames complementares, considerados imprescindíveis para se estabelecer o diagnóstico etiológico dessas doenças

INTRODUCTION: Myopathies are diseases which etiology results from structural and/or functional changes in skeletal muscle. Distal myopathies are a group of muscular pathologies in which weakness and atrophy begins and predominates in distal limbs, like hands and feet. Although it has been divided as a restrict group of diseases, other myopathies can manifest with that pattern of weakness, such nemaline myopathy and limb-girdle muscular dystrophies. Due to the scarcity of studies that described clinically the distal myopathies, this study focuses on clinical characterization of myopathies with distal pattern of weakness. METHODOLOGY: The patients were selected in the outpatient clinic for neuromuscular diseases at Professor Edgar Santos University Hospital. Those subjects were clinically evaluated through physical examination, laboratory tests, electroneuromyography, magnetic resonance (MRI) and histopathological study. RESULTS: Fifteen patients with distal pattern were analyzed, being 40% female, mean age 29.8 years, six (40 %) patients were born in the capital, Salvador-Bahia. As for the pattern of weakness distribution, seven had an exclusive distal pattern, while eight had a distal-proximal pattern. Patients were grouped according to the age of onset of symptoms, of which 11 were initiated in childhood and adolescence ( T in homozygous in exon 53 in another and one patient were diagnosed by biopsy), one with sarcoglicanopathy (mutation c.229C> T in homozygous) and one with nemaline myopathy (histopathological with the presence of nemalinic bodies). DISCUSSION: The findings identified in patients with established diagnoses were compatible with what is seen in the literature, such as clinical presentation and previously identified mutations. We highlight the pronounced distal component of the patient with sarcoglicanopathy, considered to be uncommon. In addition, the description of MRI performed in the individuals demonstrated a typical pattern. Most of the patients were not diagnosed, despite the research done with the complementary and clinical exams. CONCLUSION: The present study characterized a sample of patients with distal myopathies, corroborating that these diseases manifest themselves clinically heterogeneously. The characterization and division between groups aims to make the investigation easier, and should be done with complementary tests, considered essential to establish the etiological diagnosis of these diseases

Medical Genetics and the First Studies of the Genetics of Populations in Mexico.

Following World War II (WWII), there was a new emphasis within genetics on studying the genetic composition of populations. This probably had a dual source in the growing strength of evolutionary biology and the new international interest in understanding the effects of radiation on human populations, following the atomic bombings in Japan. These global concerns were shared by Mexican physicians. Indeed, Mexico was one of the leading centers of this trend in human genetics. Three leading players in this story were Mario Salazar Mallén, Adolfo Karl, and Rubén Lisker. Their trajectories and the international networks in human genetics that were established after WWII, paved the way for the establishment of medical and population genetics in Mexico. Salazar Mallén's studies on the distribution and characterization of ABO blood groups in indigenous populations were the starting point while Karl's studies on the distribution of abnormal hemoglobin in Mexican indigenous populations showed the relationships observed in other laboratories at the time. It was Lisker's studies, however, that were instrumental in the development of population genetics in the context of national public policies for extending health care services to the Mexican population. In particular, he conducted studies on Mexican indigenous groups contributing to the knowledge of the biological diversity of human populations according to international trends that focused on the variability of human populations in terms of genetic frequencies. From the start, however, Lisker was as committed to the reconstruction of shared languages and practices as he was to building networks of collaboration in order to guarantee the necessary groundwork for establishing the study of the genetics of human populations in Mexico. This study also allows us to place Mexican science within a global context in which connected narratives describe the interplay between global trends and national contexts.

[Application of population genetics in the field of medicine]. / Aplicación de la genética de poblaciones en el ámbito de la medicina.

Human populations follow the same evolutionary principles as other organisms, although mixed with social and cultural elements, which can result in a high prevalence of certain diseases within specific ethnic groups. In this work, the Hardy-Weinberg principle is analyzed from a medical, social and biological viewpoint to understand the evolutionary processes of autosomal recessive diseases. It can be concluded that the incidence of these diseases is inversely related to the levels of genetic variability within populations, which depends on colonization, recolonization and migration events, as well as on social conventions such as racism, social stratification and segregation.

Aplicación de la genética de poblaciones en el ámbito de la medicina / Application of population genetics in the field of medicine

Las poblaciones humanas obedecen a los mismos supuestos evolutivos que el resto de los organismos, aunque mezclados con elementos sociales y culturales que pueden promover la expresión de ciertas enfermedades en grupos étnicos específicos, causadas principalmente por la frecuente endogamia. En este trabajo se analiza el principio de Hardy-Weinberg desde un enfoque médico, social y biológico, para entender los procesos evolutivos que dan lugar a las enfermedades autosómicas recesivas. A manera de conclusión se puede señalar que la incidencia de estas enfermedades está inversamente relacionada con los niveles de la variabilidad genética en las poblaciones, variabilidad que depende de eventos de colonización, recolonización y migración, así como de convenciones sociales como el racismo, la estratificación social y la segregación.

Human populations follow the same evolutionary principles as other organisms, although mixed with social and cultural elements, which can result in a high prevalence of certain diseases within specific ethnic groups. In this work, the Hardy-Weinberg principle is analyzed from a medical, social and biological viewpoint to understand the evolutionary processes of autosomal recessive diseases. It can be concluded that the incidence of these diseases is inversely related to the levels of genetic variability within populations, which depends on colonization, recolonization and migration events, as well as on social conventions such as racism, social stratification and segregation.

Newborn screening for lysosomal diseases: current status and potential interface with population medical genetics in Latin America.

The aim of newborn screening (NBS) programs is to detect a condition in a presymptomatic baby and provide management measures which could significantly improve the natural history of the disease. NBS programs for metabolic diseases were first introduced in North America and Europe and in the 1960s for phenylketonuria, expanded a few years later to include congenital hypothyroidism, and have been growing steadily in terms of number of conditions tested for and number of countries and births covered. Lysosomal storage diseases (LSDs) are a group of around 50 genetic conditions in which a defect in a lysosomal function occurs. LSDs are progressive conditions, being usually asymptomatic at birth, but with clinical features becoming apparent in childhood, with severe manifestations in most instances, high morbidity and shortened life span. Although individually rare, the prevalence of LSDs is significant when the group is considered as a whole (around 1:4,000-1:9,000 live births). Several management techniques, including bone marrow transplantation, enzyme replacement therapy, substrate inhibition therapy, pharmacological chaperones and many other approaches are transforming the LSDs into treatable conditions. However, lack of awareness and lack of access to tests cause a significant delay between onset of symptoms and diagnosis. Several lines of evidence showing that the earlier introduction of therapy may provide a better outcome, are bringing support to the idea of including LSDs in NBS programs. Due to advances in technology, high-throughput multiplex methods are now available for mass screening of several LSDs. Pilot projects were already developed in many countries for some LSDs, with interesting results. Although some NBS in Latin America has been carried out since the 1970s, it has so far been incorporated as a public health program in only a few countries in the region. It will probably take many years before NBS is implemented in most Latin American countries with a comprehensive coverage in terms of number of diseases and number of births. Population medical genetics is the area of medical genetics that aims at the study and medical care of the population, and not of the family, which is the case for clinical or medical genetics itself. It combines different aspects of genetics: clinical genetics; human population genetics, which investigates populations according to micro-evolutionary parameters; epidemiological genetics, traditionally involved in the study of common chronic diseases of polygenic etiology, except for Mendelian diseases; and sanitary or community genetics, which stands at the interface with public health, giving support to preventive health measures. Taking into account that several LSDs were identified in a higher frequency in selected areas and/or populations, the population medical genetics approach could help to introduce the NBS for LSDs in the region, with identification of areas with higher risk for selected diseases and design of customized screening program to address specific needs. As an example of the potential of this approach, a pilot program of NBS for MPS VI was implemented in a community from North East Brazil where 13 cases of MPS VI were identified in an area with 50,000 inhabitants. This program, which will enable not only identification and early treatment of affected newborns but also carrier detection, and which would allow genetic counseling for at-risk couples, could be an alternative model for a customized NBS of LSDs to be carried out in selected regions.

Lo que se viene: la epigenética / Epigenetics is coming

A menudo se atribuye a Conrad Waddington (1905-1975) la acuñación del término epigenética en el año 1942 como la rama de la biología que estudia las interacciones causales entre los genes y sus productos que dan lugar al fenotipo. El campo de la epigenética intenta determinar cómo afectan a la función genómica, los mecanismos que regulan la manera en que los genes son procesados. Los factores epigenéticos incluyen tanto patrones espaciales, como la organización del ADN alrededor de las proteínas histónicas (cromatina), como la marcación bioquímica...(AU)

Lo que se viene: la epigenética / Epigenetics is coming

A menudo se atribuye a Conrad Waddington (1905-1975) la acuñación del término epigenética en el año 1942 como la rama de la biología que estudia las interacciones causales entre los genes y sus productos que dan lugar al fenotipo. El campo de la epigenética intenta determinar cómo afectan a la función genómica, los mecanismos que regulan la manera en que los genes son procesados. Los factores epigenéticos incluyen tanto patrones espaciales, como la organización del ADN alrededor de las proteínas histónicas (cromatina), como la marcación bioquímica...

Paleogenetical study of pre-Columbian samples from Pampa Grande (Salta, Argentina).

Ancient DNA recovered from 21 individuals excavated from burial sites in the Pampa Grande (PG) region (Salta province) of North-Western Argentina (NWA) was analyzed using various genetic markers (mitochondrial DNA, autosomal STRs, and Y chromosomal STRs). The results were compared to ancient and modern DNA from various populations in the Andean and North Argentinean regions, with the aim of establishing their relationships with PG. The mitochondrial haplogroup frequencies described (11% A, 47% B, and 42% D) presented values comparable to those found for the ancient Andean populations from Peru and San Pedro de Atacama. On the other hand, mitochondrial and Y chromosomal haplotypes were specific to PG, as they did not match any other of the South American populations studied. The described genetic diversity indicates homogeneity in the genetic structure of the ancient Andean populations, which was probably facilitated by the intense exchange network in the Andean zone, in particular among Tiwanaku, San Pedro de Atacama, and NWA. The discovery of haplotypes unique to PG could be due to a loss of genetic diversity caused by recent events affecting the autochthonous populations (establishment of the Inca Empire in the region, colonization by the Europeans).

The genetic legacy of the Transatlantic Slave Trade in the island of New Providence.

The Bahamian archipelago has been influenced by a wide array of settlers (Lucayans, Eleutherian Adventurers, British Loyalists, Creoles from the United States and African slaves) throughout its short but dynamic history. Nevertheless, the Bahamas remains poorly characterized genetically and little is known about each group's contribution to the island chain. In the current study, the population of New Providence was analyzed based on 15 autosomal STR loci routinely employed in forensic DNA fingerprinting applications. A comparison of this collection with African groups reveals similar genetic profiles to West African populations from Equatorial Guinea and Angola, possibly resulting from the importation of slaves from West African ports during the Transatlantic Slave Trade. Although the New Providence collection exhibits strong genetic affinities to the two US African American reference populations, the detection of unique alleles among them may necessitate the utilization of population-specific databases in forensic cases especially when the STR profiles include these specific variants.

Una nueva alternativa diagnóstica: estudio de las enfermedades lisosomales por métodos enzimáticos / A new diagnostic alternative: study of the lysosomal diseases by enzymatic methods

En Cuba, las enfermedades comunes que provocaban la muerte de niños entre 0 y 5 años han dejado de constituir un problema de salud, y ahora la salud pública ha dirigido su atención a otras que son causa de muerte entre neonatos, infantes, adolescentes y adultos, como son las enfermedades genéticas, y ha diseñado un programa para el desarrollo de la genética médica que permite un mayor número de diagnósticos. En estos momentos, el Centro Nacional de Genética Médica y el sistema de salud cubano, además de contar con una red de atención primaria, que comienza con el Médico de Familia, el cual se apoya ante una sospecha clínica de alguna alteración genética en los másteres y genetistas clínicos de cada municipio, cuentan con ensayos de laboratorio para el diagnóstico de 20 enfermedades lisosomales, disponibles para todo el país, lo que redundará en beneficio a los pacientes y familiares en los que exista esta alteración genética(AU)

Una nueva alternativa diagnóstica: estudio de las enfermedades lisosomales por métodos enzimáticos / A new diagnostic alternative: study of the lysosomal diseases by enzymatic methods

En Cuba, las enfermedades comunes que provocaban la muerte de niños entre 0 y 5 años han dejado de constituir un problema de salud, y ahora la salud pública ha dirigido su atención a otras que son causa de muerte entre neonatos, infantes, adolescentes y adultos, como son las enfermedades genéticas, y ha diseñado un programa para el desarrollo de la genética médica que permite un mayor número de diagnósticos. En estos momentos, el Centro Nacional de Genética Médica y el sistema de salud cubano, además de contar con una red de atención primaria, que comienza con el Médico de Familia, el cual se apoya ante una sospecha clínica de alguna alteración genética en los másteres y genetistas clínicos de cada municipio, cuentan con ensayos de laboratorio para el diagnóstico de 20 enfermedades lisosomales, disponibles para todo el país, lo que redundará en beneficio a los pacientes y familiares en los que exista esta alteración genética.

Frecuencia de enfermedades neoplásicas en familiares de pacientes con cáncer / Frecuency of neoplastic diseases in relatives in patients diagnosed with cancer

Estudio de casos y controles realizado en el Hospital General San Felipe durante los meses de Mayo y Junio del 2004. OBJETIVO: determinar la frecuencia de enfermedades neoplásicas en familiares de pacientes diagnosticados de cáncer. METODOS: Se estudiaron 220 casos, 119 con diagnóstico clínico de cáncer y 101 sin evidencia de esta enfermedad, de los primeros se eliminaron 17 por no contar con el reporte de Anatomía Patológica en el Expediente Clínico. RESULTADOS: de los 102 casos de cáncer,46 tenían antecedentes familiares positivos un total de 83 familiares de estos padecían o habían padecido de algún tipo de enfermedad neoplásica, ya que algunos pacientes tenían más de un familiar afectado. De los 101 pacientes positivos sin cáncer hubo 25 de ellos con antecedentes positivos de enfermedades neoplásicas y un total de 35 familiares afectados. Del grupo con cáncer hubo 18 casos entre hermanos hijos y sobrinos, en cambio para el grupo control se presentaron 3 casos únicamente en este mismo grupo de familiares. CONCLUSIONES: los pacientes diagnosticados de cáncer tienen mas alta frecuencia de enfermedades neoplásicas en sus familias comparados con pacientes que sufren de otras enfermedades sin evidencia clínica ni patológica de cáncer. Los parientes en primer grado de pacientes con cáncer son más frecuentemente afectados de enfermedades neoplásicas, que los parientes en primer grado de pacientes que no presentan cáncer...(AU)