RESUMO
Heart disease is the cause of sudden death in more than 80% of cases. Ischemic heart disease is the cause for 90% of all sudden cardiac deaths, while in the remaining 10% of cases, heart diseases have a hereditary origin and comprise a wide spectrum of disorders that include cardiomyopathies and channelopathies. The aim of this review is to highlight the importance of genetic counseling for patients with hereditary cardiovascular disease and its evaluation by a multidisciplinary team.
La cardiopatía es la causa de muerte súbita en más del 80% de casos. La cardiopatía isquémica es responsable en el 90% del total de las muertes súbitas cardiacas, mientras que en el 10% de casos restantes, las cardiopatías tienen un origen hereditario y comprenden un amplio espectro de trastornos que incluyen a las cardiomiopatías y las canalopatías. El objetivo de esta revisión es poner en evidencia la importancia del asesoramiento genético de los pacientes con enfermedad cardiovascular hereditaria y su evaluación a través de un equipo multidisciplinario.
RESUMO
El cáncer de próstata es, desde el punto de vista molecular, biológicamente heterogéneo debido a la diversidad de alteraciones moleculares inter e intratumorales, siendo además un proceso genómico dinámico y evolutivo. Con el desarrollo de nuevas técnicas moleculares, como el secuenciamiento génico, microarreglos, estudios epigenenómicos, entre otros, se ha podido caracterizar molecularmente al cáncer de próstata, encontrándose diferencias incluso entre los diferentes estadíos de la enfermedad.
To understand the term genomic heterogeneity in prostate cancer, we must understand the clonal genomic evolution of cancer, as well as knowing that it is a dynamic and evolutionary phenomenon. Knowing the genome of prostate cancer not only allows us to have a vision over time of the genomic alterations that occur during its different stages, but also to learn about the mechanisms of metastasis. In addition, knowing the hereditary component of prostate cancer allows the evaluation of patients and to be able to identify if we are dealing with a family at risk.
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INTRODUCTION: Cancer is the second leading cause of death worldwide, with 70% of cancer deaths occurring in low- or middle- income countries. To mitigate the mortality of this disease, it is recommended the evaluation of multiple high-penetrance genes. METHODS: We used a multi-gene panel testing to identify germline variants in a unique case of a breast cancer patient with a family history of five different neoplasm types. The patient, at the age of 50 years, was diagnosed with a high-grade cribriform ductal carcinoma in situ in her left breast. RESULTS: We identified two heterozygous mutations, one classified as pathogenic/likely pathogenic in RAD50 and the other classified as a variant of uncertain significance (VUS) in ATM. CONCLUSION: In conclusion, the use of the multi-gene panel leads to the identification of a double heterozygous mutation in RAD50 and ATM in a breast cancer patient from a Peruvian family with several cancer types. This data helps our physician team and the patient to choose a treatment following the post-test genetic counseling.
Assuntos
Neoplasias da Mama , Hidrolases Anidrido Ácido/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Proteínas de Ligação a DNA/genética , Feminino , Aconselhamento Genético , Humanos , Pessoa de Meia-Idade , Mutação , PeruRESUMO
El número de enfermedades genéticas se estima que podrían ser más de 10 000 condiciones diferentes, afectando alrededor del 6-8% de la población. La presente revisión nos muestra la importancia del descubrimiento de las variantes patogénicas en nuestro genoma que nos permite conocer con mayor precisión cuales son los mecanismos fisiopatológicos, y por lo tanto conocer puntos dianas susceptibles de modificaciones, mediante diferentes estrategias terapéuticas para poder palear los síntomas y signos, aumentar la expectativa de vida, mejorando así la calidad de vida de los pacientes que tienen algunas de estas enfermedades genéticas. Las diferentes terapias que existen en la actualidad son muy diversas como fármacos de uso en patologías comunes, terapia nutricional, fórmulas especiales, terapias de reemplazo enzimático, trasplante de órganos y células hematopoyéticas, reducción de sustrato, oligonucleótidos y la terapia génica. Al ser las enfermedades genéticas clínicamente heterogéneas, abre la posibilidad de poder investigar cada vez más nuevas estrategias en un mayor número de enfermedades que en la actualidad están olvidadas.
Today, the number of genetic diseases is around 10000 conditions, affecting to 6%-8% of all populations. This review shows us how the discovery of genetic variants in our genome, this facilitated to know with precision about the mechanisms physiopathological, and hence to recognize those target points susceptible to modifications, through therapeutical strategies different with palliative proposals, increase life expectancy, or improve qualities of life. These therapies are diverse, using drugs for polygenic diseases, nutritional therapy, special formulas, enzyme replacement therapies, hematopoietic stem cell transplant, substrate reduction, oligonucleotides, and gene therapy. These genetic diseases are heterogeneous clinically with a very low frequency; nevertheless, open to the possibility of research in new strategies for more genetic disease, that today, furthermore, are orphans.
RESUMO
Mr. Editor, The National Comprehensive Cancer Network (NCCN) has determined that when a syndrome of predisposition to cancer is suspected, it is necessary to refer the patient for genetic evaluation because of the implications for diagnosis and management, as well as follow-up in the family (1). The genetic evaluation includes the description of the personal/family history and the request for the corresponding genetic study.
Sr. Editor, La Red Nacional Integral del Cáncer (NCCN) ha determinado que ante la sospecha de un síndrome de predisposición al cáncer, es necesario referir al paciente a evaluación genética debido a las implicancias en el diagnóstico y manejo, así como el seguimiento en sus familiares (1). La evaluación genética incluye la descripción de los antecedentes personales/familiares y la solicitud del estudio genético correspondiente.
Assuntos
Neoplasias Gastrointestinais , Síndromes Neoplásicas Hereditárias , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/genética , Aconselhamento Genético , Predisposição Genética para Doença , Testes Genéticos , Humanos , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genéticaRESUMO
Resumen Los avances en la investigación clínica, genética y molecular del cáncer colorrectal (CCR) realizados durante los últimos años han permitido su detección temprana, así como su tratamiento oportuno. Sin embargo, uno de los mayores desafíos de esta enfermedad es su naturaleza heterogénea y la participación de diversas vías moleculares en su carcinogénesis. La implementación de las tecnologías ómicas -como la genómica, la proteómica, la transcriptómica y la epigenómica- en la investigación biomédica de pacientes con CCR hereditario ha permitido identificar nuevos genes o polimorfismos de nucléotido único (SNP, por su sigla en inglés) que afectan la expresividad del cáncer. Por otra parte, las herramientas bioinformáticas han contribuido a generar nuevas hipótesis sobre el CCR, orientando el abordaje de estos pacientes hacia una medicina personalizada. Este avance científico y tecnológico tiene un impacto en la salud, tanto a nivel individual como colectivo, por lo que es importante reflexionar sobre la viabilidad de desarrollar estrategias de salud pública para la implementación de un programa integral y genético de prevención y manejo del cáncer en Perú, en especial del CCR hereditario.
Abstract Progress in clinical, genetic and molecular research of colorectal cancer (CRC) in recent years has allowed its early detection and timely and targeted treatment. However, one of the greatest challenges is the heterogeneous nature of CRC and the involvement of various molecular pathways in its carcinogenesis. The implementation of technologies known as omics -such as genomics, proteomics, transcriptomics and epigenomics- in biomedical research on patients with hereditary CRC has allowed the identification of new genes or single nucleotide polymorphisms (SNPs) that affect the expressivity of cancer. Bioinformatics tools have also contributed to generate new hypotheses about CRC, guiding the approach to these patients towards personalized medicine. This scientific and technological progress has an impact on health, both at the individual and the collective level, so it is important to reflect on the feasibility of developing public health strategies for the implementation of a comprehensive and genetic program for the prevention and treatment of cancer in Peru, especially hereditary CRC.
Assuntos
Humanos , Neoplasias Colorretais , Saúde Pública , GenéticaRESUMO
La Hipertensión arterial pulmonar (HAP) es una enfermedad heterogénea donde los genes juegan un rol sumamente importante. La HAP hereditaria (HAPh) se define como una condición genética de patrón de herencia autosómico dominante, de penetrancia incompleta, de expresividad variable, que presenta un fenómeno de anticipación y que agrupa a los casos de HAP familiar definido por la presencia de dos o más miembros de la familia con HAP con o sin variante germinal identificada y a los casos de HAP idiopática que corresponde a los casos aislados en la familia con una variante germinal identificada. Para establecer el diagnóstico de HAPh, es necesario confirmar el diagnóstico en al menos dos familiares (HAPf) o identificar la variante germinal en un caso aislado en la familia (HAPi).
Pulmonary arterial hypertension (PAH) is a heterogeneous disease where genes play an important role. Hereditary PAH (PAH) is defined as a genetic condition of autosomal dominant manner, incomplete penetrance, variable expressivity, and which cases of familial PAH are defined by the presence of two or more family members with PAH with or without an identified germline variant and cases of idiopathic PAH corresponding to isolated cases in the family with an identified germline variant. To establish the diagnosis of hAPH, it is necessary to confirm the diagnosis in at least two relatives (HAPf) or identify the germline variant in an isolated case in the family (HAPi).
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BACKGROUND: Prevalence of maturity-onset diabetes of the young (MODY) is estimated between 1 and 2% of all diabetes cases. In Latin-America little information has been described about the frequency of the disease, perhaps due to limited access to genetic studies. CASE PRESENTATION: We present the case of a male patient with a history of two years of fatigue, mild hyperglycemia and intermittent polyuria, accompanied by a recent history of weight loss. He was diagnosed initially as type 2 diabetes, but in the follow-up as a patient with type 1 diabetes. He required relatively low doses of insulin and was evaluated in the endocrinology service at a hospital in Lima. The results of glucose, insulin and C-peptide in the oral glucose tolerance test (OGTT) performed were not consistent with a type 1 diabetes. Moreover, the age of the patient and the clinical characteristics did not strongly suggest a diagnosis of type 2 diabetes either. These clinical features had prompted us to carry out the genetic study. The genetic test performed with a genetic MODY panel through a massive sequencing. Heterozygous pathogenic for a variant in GCK gene was found (c.629 T > C, p.Met210Thr.). His parents were negative for this variant after performed the genetic test. CONCLUSIONS: This is the first case of MODY for a pathogenic variant in the GCK gene reported in Perú. The genetic evaluation of a clinical suspicion of MODY is important to confirm the diagnosis and establish an adequate treatment in patients.
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This review aims to present the genetic, clinical and diagnostic aspects of Lynch syndrome, as well as providing the most relevant information about genetic counseling in these patients and the current recommendations for their surveillance.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Algoritmos , Biomarcadores Tumorais , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/história , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Reparo de Erro de Pareamento de DNA/genética , DNA de Neoplasias/genética , Diagnóstico Diferencial , Endoscopia Gastrointestinal , Genes Neoplásicos , Estudos de Associação Genética , Aconselhamento Genético , Heterogeneidade Genética , História do Século XIX , História do Século XX , Humanos , Instabilidade de Microssatélites , Modelos Genéticos , Síndromes Neoplásicas Hereditárias/diagnóstico , Penetrância , Risco , Medição de RiscoRESUMO
La asesoría genética en cáncer permite reducir la morbimortalidad en pacientes con cáncer hereditario y sus familiares mediante un manejo multidisciplinario que establezca medidas preventivas, detección precoz y control de riesgos.