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RESUMEN Introducción: Las hemoglobinopatías y dentro de ellas la anemia falciforme, constituyen las alteraciones monogénica más frecuentes en el mundo, con un patrón de herencia autosómico recesivo; en Cuba es la enfermedad molecular más frecuente. El Programa de Prevención de hemoglobinopatías se basa en el pesquisaje mediante el estudio de Electroforesis de hemoglobina a todas las gestantes aplicándose en Cuba desde 1983. Objetivo: Diseñar una estrategia educativa preventiva para las parejas de riesgo, partir de los resultados del programa de prevención de hemoglobinopatías en la provincia de Pinar del Río durante el periodo 2013-2018. Métodos: Se realizó un estudio descriptivo, retrospectivo y de corte longitudinal al total de gestantes captadas desde el año 2013 al 2018 a las que se les realizó la Electroforesis de hemoglobina más aquellas en las que su condición era conocida por estudio en embarazos anteriores. Se calculó el porcentaje de las portadoras, así como las homocigóticas para el alelo S y C, a todos estos casos se estudió la pareja. Los resultados se presentaron en tablas. Resultados: La frecuencia de portadoras de hemoglobina S y C fue de 1,49 % y 0,30 % respectivamente, el 95,1 % de los esposos fueron estudiados, existieron 34 parejas de riesgo a las cuales se les realizaron estudio molecular fetal, previo asesoramiento genético. Conclusiones: Se les brindó asesoramiento genético y estudio molecular fetal a las parejas de alto riesgo, corroborando la necesidad de mejorar la educación de la población sobre la enfermedad.
ABSTRACT Introduction: hemoglobinopathies, including sickle cell disease, are the most frequent monogenic alterations in the world, with an autosomal recessive inheritance pattern. In Cuba, it is the most frequent molecular disease. The Program for the Prevention of Hemoglobinopathies is based on research through the study of hemoglobin electrophoresis in all pregnant women and has been applied in Cuba since 1983. Objective: to design a preventive educational strategy for couples at risk based on the results of the program for the prevention of hemoglobinopathies in Pinar del Río province during the period of 2013-2018. Methods: a descriptive, retrospective and longitudinal study was carried out with all pregnant women who had undergone hemoglobin electrophoresis during 2013-2018, along with those whose condition was known from previous pregnancies. The percentage of carriers was calculated, as well as the homozygous for S and C allele, to all these cases the couple was studied. The results were presented in tables. Results: the frequency of carriers of hemoglobin S and C was 1,49 % and 0,30 % respectively, 95.1 % of the spouses were studied, there were 34 couples at risk who underwent fetal molecular study, after genetic counseling. Conclusions: genetic counseling and fetal molecular study were provided to high-risk couples, corroborating the need to improve the education of the population regarding this disease.
ABSTRACT
El objetivo de este trabajo fue caracterizar demográfica y molecularmente las familias con diagnóstico de síndrome de Lynch en base a estudios genéticos. Se utilizó la base prospectiva del Registro de Epidemiología Molecular de Cáncer Colorrectal (REM-CCR) del Hospital Italiano de Buenos Aires (Clinical trials.gov NCT02781337). El criterio de inclusión fue que tuvieran hecho un estudio genético entre 1996 y 2017 (secuenciación y/o determinación de grandes rearreglos de al menos un gen reparador de error de apareamiento). Se analizaron 50 familias con los criterios de Amsterdam. En 23 (46%) se identificaron variantes patogénicas (n=19) y probablemente patogénicas (n=2). El 28.6% de las variantes patogénicas fueron originalmente descritas en esta serie, entre ellas la variante c.1911del en el exón 12 de MSH2 identificada en una familia con agregación de cáncer de mama. Fue identificada una mutación fundadora de Piamonte, Italia (c.2252_2253del). Los genes afectados incluyeron MSH2 (13 variantes) MLH1 (9 variantes) y PMS2 (1 variante). La tasa de detección de mutaciones fue del 46%. Entre las familias con mutación identificada (n=23), se detectó una edad mediana de inicio del cáncer menor (46 vs. 50 años, p=0.02) y mayor incidencia de tumores extra-colorrectales (90.5% vs. 45.8%, p <0.01), que las 27 sin mutaciones. La implementación de estudios genéticos permitió caracterizar variables demográficas en base a la identificación de mutaciones germinales asociadas al síndrome de Lynch, identificándose dos grupos diferenciados por la edad de afectación y la incidencia de tumores extracolónicos (AU)
The aim of this study was to characterize demographically and molecularly families diagnosed with Lynch syndrome based on genetic studies. Families with a genetic study performed between 1996 and 2017 (sequencing and/or determination of large rearrangements of a mismatch repair gene at least) were selected from the prospective database REM-CCR of Hospital Italiano de Buenos Aires (Clinical trials. Gov NCT02781337). Fifty families fulfilled Amsterdam criteria were analyzed. Pathogenic variants were found in 23 out of 50 (46%) families, being 21 pathogenic and 2 likely pathogenic. The 28.6% of the pathogenic variants were originally described in this series. Among them, the variant c.1911del in MSH2 in a family with breast cancer aggregation and a founder MLH1 mutation from Piedmont, Italy (c.2252_2253del) were identified. Affected genes include MSH2 (13 variants), MLH1 (9 variants), PMS2 (1 variant). Mutations detection rates was 46%. Those families with an identified mutation (n=23) had a lower median age of cancer onset (46 vs. 50 years, p=0.02) and a higher incidence of extra-colorectal tumors (90.5% vs. 45.8%, p<0.01) than those without identified mutations (n=27). The implementation of genetic studies allowed characterizing demographic variables based on the identification of germline mutations associated with Lynch syndrome. Two groups, Síndrome de Lynch: impacto de la caracterización de familias en base a estudios genéticos 3 differentiated by the age of cancer onset and the incidence of extracolonic tumors were characterized (AU)
Subject(s)
Humans , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Genetic Association Studies , Germ-Line Mutation , Observational StudyABSTRACT
Este artigo aborda as dificuldades de inserir a genética médica como parte do Sistema Único de Saúde (SUS) no Brasil. Em 2009, foi instituída no Brasil a Política Nacional de Atenção Integral em Genética Médica, cujo pilar central seria o aconselhamento genético. Porém, são problemas estratégicos para a implementação dessa política a falta de programas de formação em aconselhamento genético, o desconhecimento acerca de quantos profissionais existem para prestar esse aconselhamento e o provável baixo número de profissionais disponíveis. É desejável uma atuação conjunta dos Ministérios da Saúde e da Educação para ampliar a educação em genética e a formação em aconselhamento genético para todas as profissões no campo da saúde. Além disso, é essencial a inclusão da genética em programas como o Saúde da Família, que permitirá um mapeamento da incidência das doenças genéticas no país e a implementação de aconselhamento genético apesar do grande território e da heterogeneidade populacional do Brasil. Finalmente, a inserção da genética médica no SUS depende do engajamento de profissionais médicos e não médicos no trabalho em equipes horizontais, com alteração da tradicional hierarquia da atenção à saúde.
The present article deals with the difficulties of introducing medical genetics as part of the Brazilian public Unified Health System (SUS). A national policy of comprehensive care in medical genetics was established in 2009, having genetic counseling as a central pillar. However, there are strategic limitations to the implementation of this policy: a dearth of genetic counseling training programs, the lack of knowledge concerning the number of professionals available to provide genetic counseling, and the likely low number of professionals available for the job. A joint effort by the ministries of health and education is desirable to foster genetics and genetic counseling training for all health professions. In addition, genetics must be introduced in government programs such as the Family Health Program (Saúde da Família), a measure that would allow a mapping of the incidence of genetic diseases in the country and the implementation of genetic counseling despite the size of the territory and the population heterogeneity. Lastly, the introduction of medical genetics as part of the SUS depends on the engagement of medical and nonmedical professionals in horizontal teamwork, with a change in the hierarchy that has traditionally been at the foundations of health care.