Miopatías RYR1 en la infancia: correlación fenotipo-genotipo e incidencia / RYR1 myopathies in childhood: phenotype-genotype correlation and incidence

Introducción: Las miopatías relacionadas con el receptor de rianodina de tipo 1 (RYR1-RM) constituyen la categoría más frecuente de miopatías congénitas. La introducción de técnicas genéticas ha cambiado el paradigma diagnóstico y sugiere la prioridad de estudios moleculares sobre biopsias. Este estudio busca explorar las características clinicoepidemiológicas de pacientes con variantes del gen RYR1 en un hospital pediátrico de tercer nivel con el objetivo de ampliar la comprensión de la correlación genotipo-fenotipo en las RYR1-RM. Pacientes y métodos: Estudio observacional, descriptivo y transversal, de pacientes menores de 14 años con síntomas miopáticos y variantes potencialmente patógenas del gen RYR1 entre enero de 2013 y diciembre de 2023, considerando variables como sexo, edad, desarrollo motor, variantes genéticas, patrón de herencia y otras manifestaciones. Todas las variables fueron tabuladas frente a la variante genética. Resultados: De los nueve pacientes incluidos, la incidencia estimada fue de aproximadamente 1/10.000 nacidos vivos. La mediana en el momento del diagnóstico fue de 6 años, con una variabilidad fenotípica significativa. Se observaron síntomas comunes, como debilidad y retraso del desarrollo motor. Las variantes genéticas afectaron al gen RYR1 de manera diversa, y hubo cinco variantes previamente no descritas. La biopsia muscular se realizó en cinco pacientes, en dos de ellos de tipo miopatía central core; en uno, multiminicore; en uno, desproporción congénita de fibras; y en otro, de patrón inespecífico. Conclusiones: Las RYR1-MR de nuestra serie ofrecieron variabilidad fenotípica y de afectación, con una incidencia en nuestra área de en torno a 1/10.000 recién nacidos. La mayoría de los casos fueron varones, de variantes missense dominantes. Aportamos cinco variantes genéticas no descritas con anterioridad.(AU)

Introduction: Ryanodine receptor type 1-related myopathies (RYR1-RM) represent the most prevalent category of congenital myopathies. The introduction of genetic techniques has shifted the diagnostic paradigm, suggesting the prioritization of molecular studies over biopsies. This study aims to explore the clinical and epidemiological characteristics of patients with RYR1 gene variants in a tertiary pediatric hospital, intending to enhance the understanding of the genotype-phenotype correlation in RYR1-RM. Patients and methods: An observational, descriptive, and cross-sectional study was conducted on patients under 14 years old with myopathic symptoms and potentially pathogenic RYR1 gene variants from January 2013 to December 2023. Variables such as gender, age, motor development, genetic variants, inheritance pattern, and other manifestations were considered. All variables were tabulated against the genetic variant. Results: Of the nine included patients, the estimated incidence was approximately 1 in 10,000 live births. The median age at diagnosis was six years, with significant phenotypic variability. Common symptoms such as weakness and delayed motor development were observed. Genetic variants affected the RYR1 gene diversely, including five previously undescribed variants. Muscle biopsy was performed in five patients, revealing central core myopathy in two, multiminicore in one, congenital fiber-type disproportion in one, and a nonspecific pattern in another.(AU)

La importancia de la genética en el estudio de la hipertrigliceridemia / The importance of genetics in the study of hypertriglyceridemia

La hipertrigliceridemia engloba un conjunto de trastornos lipídicos comunes en la práctica clínica, generalmente definidos como una concentración superior a 150mg/dL en ayunas. Existen diversas clasificaciones de la gravedad de la hipertrigliceridemia en función de sus valores séricos, considerándose por norma general moderada cuando los niveles son inferiores a 500mg/dL y severa cuando son mayores de 1.000mg/dL. Su importancia radica en su asociación con otras alteraciones del perfil lipídico, contribuyendo al aumento del riesgo cardiovascular y de pancreatitis aguda, fundamentalmente con concentraciones superiores a 500mg/dL.(AU)

Hypertriglyceridemia encompasses a set of lipid disorders common in clinical practice, generally defined as a fasting concentration above 150mg/dL. There are various classifications of the severity of hypertriglyceridaemia based on serum values, with levels generally considered moderate when below 500mg/dL and severe when above 1000mg/dL. Its importance lies in its association with other alterations in the lipid profile, contributing to increased cardiovascular risk and increased risk of acute pancreatitis, mainly with concentrations above 500mg/dL.(AU)

The potential influence of genome-wide adaptive divergence on conservation translocation outcome in an isolated greater sage-grouse population.

Conservation translocations are an important conservation tool commonly employed to augment declining or reestablish extirpated populations. One goal of augmentation is to increase genetic diversity and reduce the risk of inbreeding depression (i.e., genetic rescue). However, introducing individuals from significantly diverged populations risks disrupting coadapted traits and reducing local fitness (i.e., outbreeding depression). Genetic data are increasingly more accessible for wildlife species and can provide unique insight regarding the presence and retention of introduced genetic variation from augmentation as an indicator of effectiveness and adaptive similarity as an indicator of source and recipient population suitability. We used 2 genetic data sets to evaluate augmentation of isolated populations of greater sage-grouse (Centrocercus urophasianus) in the northwestern region of the species range (Washington, USA) and to retrospectively evaluate adaptive divergence among source and recipient populations. We developed 2 statistical models for microsatellite data to evaluate augmentation outcomes. We used one model to predict genetic diversity after augmentation and compared these predictions with observations of genetic change. We used the second model to quantify the amount of observed reproduction attributed to transplants (proof of population integration). We also characterized genome-wide adaptive divergence among source and recipient populations. Observed genetic diversity (HO = 0.65) was higher in the recipient population than predicted had no augmentation occurred (HO = 0.58) but less than what was predicted by our model (HO = 0.75). The amount of shared genetic variation between the 2 geographically isolated resident populations increased, which is evidence of periodic gene flow previously assumed to be rare. Among candidate adaptive genes associated with elevated fixation index (FST) (143 genes) or local environmental variables (97 and 157 genes for each genotype-environment association method, respectively), we found clusters of genes with related functions that may influence the ability of transplants to use local resources and navigate unfamiliar environments and their reproductive potential, all possible reasons for low genetic retention from augmentation.

Influencia potencial de la divergencia adaptativa a nivel genoma sobre el resultado de la reubicación para conservación en una población aislada de urogallo mayor Resumen Las reubicaciones para conservación son una herramienta importante que se usa con frecuencia para aumentar las poblaciones en declinación o reestablecer las poblaciones erradicadas. Una de las metas de este aumento es incrementar la diversidad genética y reducir el riesgo de depresión endogámica (es decir, rescate genético). Sin embargo, la introducción de individuos de una población con divergencia significativa puede perturbar los rasgos coadaptados y reducir la aptitud local (es decir, depresión exogámica). La información genética es cada vez más accesible para las especies silvestres y puede proporcionar conocimiento único con respecto a la presencia y retención de la variación genética introducida a partir del aumento como un indicador de eficiencia y las similitudes adaptativas como un indicador de la idoneidad de la población de origen y la receptora. Usamos dos conjuntos de datos genéticos para evaluar el aumento de las poblaciones aisladas del urogallo mayor (Centrocercus urophasianus) en la región noroeste de la distribución de la especie (Washington, EUA) y para evaluar de forma retrospectiva la divergencia adaptativa entre la población de origen y la receptora. Desarrollamos dos modelos estadísticos para los datos microsatelitales para así evaluar los resultados del aumento. Usamos un modelo para predecir la diversidad genética después del aumento y comparamos estas predicciones con observaciones del cambio genético. Usamos el segundo modelo para cuantificar el aumento de la reproducción observada atribuida a las reubicaciones (evidencia de la integración poblacional). También caracterizamos la divergencia adaptativa a nivel genoma entre la población de origen y la población receptora. La diversidad genética observada (HO = 0.65) fue mayor de lo que se predijo en la población receptora de no haber ocurrido el aumento (HO = 0.58) pero menor de lo que se predijo en nuestro modelo (HO = 0.75). El aumento de la variación genética compartida entre las dos poblaciones residentes geográficamente aisladas incrementó, lo cual es evidencia de un flujo génico periódico que antes se supuso casi no ocurría. Entre los genes adaptativos candidatos asociados a una FST elevada (143 genes) o a variables ambientales locales (97 y 157 genes para cada método de asociación entre el ambiente y el genotipo, respectivamente) encontramos grupos de genes con funciones relacionadas que pueden influir sobre la habilidad de cada reubicación para usar recursos locales y navegar ambientes desconocidos y su potencial reproductivo, todas posibles razones para la baja retención genética en el aumento.

Diagnóstico genético de la hipoacusia neurosensorial infantil / Genetic diagnosis of childhood sensorineural hearing loss

Introducción: La hipoacusia neurosensorial (HNS) congénita o de inicio precoz es una de las enfermedades hereditarias más frecuentes en nuestro medio y es la deficiencia sensorial más frecuente. Es importante realizar un estudio etiológico de la hipoacusia y el estudio genético mediante la secuenciación de nueva generación (NGS) es la prueba con mayor rendimiento diagnóstico. Nuestro estudio muestra los resultados genéticos obtenidos en una serie de pacientes con HNS congénita/de inicio precoz bilateral. Material y método: Se incluyeron 105 niños diagnosticados de HNS bilateral a los que se les realizó un estudio genético entre los años 2019 y 2022. El estudio genético consistió en una secuenciación masiva del exoma completo, filtrando el análisis para los genes incluidos en un panel virtual de hipoacusia con 244 genes. Resultados: Se obtuvo un diagnóstico genético en 48% (50/105) de los pacientes. Se detectaron variantes patogénicas y probablemente patogénicas en 26 genes diferentes, siendo los genes más frecuentemente afectados el gen GJB2, USH2A y STRC. De las variantes detectadas 52% (26/50) se asociaron a una hipoacusia no sindrómica, 40% (20/50) una hipoacusia sindrómica y 8% restante (4/50) se podían asociar tanto a una hipoacusia sindrómica como no sindrómica. Conclusiones: El estudio genético constituye una parte fundamental del diagnóstico etiológico de la HNS bilateral. Nuestra serie muestra que el estudio genético de la hipoacusia mediante NGS tiene un alto rendimiento diagnóstico y nos proporciona información de gran utilidad en la práctica clínica.(AU)

Introduction: Congenital/early-onset sensorineural hearing loss (SNHL) is one of the most common hereditary disorders in our environment. There is increasing awareness of the importance of an etiologic diagnosis, and genetic testing with next-generation sequencing (NGS) has the highest diagnostic yield. Our study shows the genetic results obtained in a cohort of patients with bilateral congenital/early-onset SNHL. Materials and methods: We included 105 children with bilateral SNHL that received genetic testing between 2019 and 2022. Genetic tests were performed with whole exome sequencing, analyzing genes related to hearing loss (virtual panel with 244 genes). Results: 48% (50/105) of patients were genetically diagnosed. We identified pathogenic and likely pathogenic variants in 26 different genes, and the most frequently mutated genes were GJB2, USH2A and STRC. 52% (26/50) of variants identified produced non-syndromic hearing loss, 40% (20/50) produced syndromic hearing loss, and the resting 8% (4/50) could produce both non-syndromic and syndromic hearing loss. Conclusions: Genetic testing plays a vital role in the etiologic diagnosis of bilateral SNHL. Our cohort shows that genetic testing with NGS has a high diagnostic yield and can provide useful information for the clinical workup of patients.(AU)

Enfermedad de Hirschsprung no sindrómica por variante en el gen RET / Non-syndromic Hirschsprung’s disease as a result of a RET gene variant

Introducción: La enfermedad de Hirschsprung (EH) se caracterizapor la ausencia de células ganglionares en los plexos submucoso y mientérico del intestino grueso, resultante de deficiencias en la migracióny diferenciación de las células de la cresta neural entérica durante laembriogénesis. Es una condición multifactorial, con más de 11 genesidentificados en su patogénesis, incluyendo el protooncogén RET.Caso clínico: Se presenta el caso de dos hermanos con EH de colontotal, cuyo padre también padeció la enfermedad, y en quien se encontróuna variante potencialmente patogénica en el gen RET.Comentarios: El diagnóstico prenatal mediante pruebas genéticaspermite decisiones informadas y la planificación de cuidados para elneonato afectado, reduciendo demoras en el diagnóstico y tratamiento,y minimizando las complicaciones a largo plazo. La identificación demutaciones como la variante en el gen RET destaca la importancia delenfoque genético en la comprensión y manejo de la EH.(AU)

Introduction: Hirschsprung’s disease (HD) is characterized by theabsence of ganglion cells in the submucosal and myenteric plexuses ofthe colon as a result of disorders in the migration and differentiationof enteric neural crest cells during embryogenesis. It is a cross-factorcondition, with more than 11 genes identified in its pathogenesis, including the RET proto-onco gene.Case report: We present the case of two siblings with total colonHD where a potentially pathogenic variant of the RET gene was found.Their father also had this condition.Discussion: Prenatal diagnosis through genetic testing allows forinformed decisions and care planning for the newborn, thus reducin delayed diagnosis and treatment, and minimizing long-term complications. Mutations such as the RET gene variant highlight the importanceof the genetic approach in understanding and managing HD.(AU)

Guidelines on the Diagnosis and Treatment of Hypertrophic Cardiomyopathy ­ 2024 / Diretriz sobre Diagnóstico e Tratamento da Cardiomiopatia Hipertrófica ­ 2024

Hypertrophic cardiomyopathy (HCM) is a form of genetically caused heart muscle disease, characterized by the thickening of the ventricular walls. Diagnosis requires detection through imaging methods (Echocardiogram or Cardiac Magnetic Resonance) showing any segment of the left ventricular wall with a thickness > 15 mm, without any other probable cause. Genetic analysis allows the identification of mutations in genes encoding different structures of the sarcomere responsible for the development of HCM in about 60% of cases, enabling screening of family members and genetic counseling, as an important part of patient and family management. Several concepts about HCM have recently been reviewed, including its prevalence of 1 in 250 individuals, hence not a rare but rather underdiagnosed disease. The vast majority of patients are asymptomatic. In symptomatic cases, obstruction of the left ventricular outflow tract (LVOT) is the primary disorder responsible for symptoms, and its presence should be investigated in all cases. In those where resting echocardiogram or Valsalva maneuver does not detect significant intraventricular gradient (> 30 mmHg), they should undergo stress echocardiography to detect LVOT obstruction. Patients with limiting symptoms and severe LVOT obstruction, refractory to beta-blockers and verapamil, should receive septal reduction therapies or use new drugs inhibiting cardiac myosin. Finally, appropriately identified patients at increased risk of sudden death may receive prophylactic measure with implantable cardioverter-defibrillator (ICD) implantation.

La miocardiopatía hipertrófica (MCH) es una forma de enfermedad cardíaca de origen genético, caracterizada por el engrosamiento de las paredes ventriculares. El diagnóstico requiere la detección mediante métodos de imagen (Ecocardiograma o Resonancia Magnética Cardíaca) que muestren algún segmento de la pared ventricular izquierda con un grosor > 15 mm, sin otra causa probable. El análisis genético permite identificar mutaciones en genes que codifican diferentes estructuras del sarcómero responsables del desarrollo de la MCH en aproximadamente el 60% de los casos, lo que permite el tamizaje de familiares y el asesoramiento genético, como parte importante del manejo de pacientes y familiares. Varios conceptos sobre la MCH han sido revisados recientemente, incluida su prevalencia de 1 entre 250 individuos, por lo tanto, no es una enfermedad rara, sino subdiagnosticada. La gran mayoría de los pacientes son asintomáticos. En los casos sintomáticos, la obstrucción del tracto de salida ventricular izquierdo (TSVI) es el trastorno principal responsable de los síntomas, y su presencia debe investigarse en todos los casos. En aquellos en los que el ecocardiograma en reposo o la maniobra de Valsalva no detecta un gradiente intraventricular significativo (> 30 mmHg), deben someterse a ecocardiografía de esfuerzo para detectar la obstrucción del TSVI. Los pacientes con síntomas limitantes y obstrucción grave del TSVI, refractarios al uso de betabloqueantes y verapamilo, deben recibir terapias de reducción septal o usar nuevos medicamentos inhibidores de la miosina cardíaca. Finalmente, los pacientes adecuadamente identificados con un riesgo aumentado de muerte súbita pueden recibir medidas profilácticas con el implante de un cardioversor-desfibrilador implantable (CDI).

A cardiomiopatia hipertrófica (CMH) é uma forma de doença do músculo cardíaco de causa genética, caracterizada pela hipertrofia das paredes ventriculares. O diagnóstico requer detecção por métodos de imagem (Ecocardiograma ou Ressonância Magnética Cardíaca) de qualquer segmento da parede do ventrículo esquerdo com espessura > 15 mm, sem outra causa provável. A análise genética permite identificar mutações de genes codificantes de diferentes estruturas do sarcômero responsáveis pelo desenvolvimento da CMH em cerca de 60% dos casos, permitindo o rastreio de familiares e aconselhamento genético, como parte importante do manejo dos pacientes e familiares. Vários conceitos sobre a CMH foram recentemente revistos, incluindo sua prevalência de 1 em 250 indivíduos, não sendo, portanto, uma doença rara, mas subdiagnosticada. A vasta maioria dos pacientes é assintomática. Naqueles sintomáticos, a obstrução do trato de saída do ventrículo esquerdo (OTSVE) é o principal distúrbio responsável pelos sintomas, devendo-se investigar a sua presença em todos os casos. Naqueles em que o ecocardiograma em repouso ou com Manobra de Valsalva não detecta gradiente intraventricular significativo (> 30 mmHg), devem ser submetidos à ecocardiografia com esforço físico para detecção da OTSVE.   Pacientes com sintomas limitantes e grave OTSVE, refratários ao uso de betabloqueadores e verapamil, devem receber terapias de redução septal ou uso de novas drogas inibidoras da miosina cardíaca. Por fim, os pacientes adequadamente identificados com risco aumentado de morta súbita podem receber medida profilática com implante de cardiodesfibrilador implantável (CDI).

Pregnancy in women with dilated cardiomyopathy genetic variants.

INTRODUCTION AND OBJECTIVES: Limited information is available on the safety of pregnancy in patients with genetic dilated cardiomyopathy (DCM) and in carriers of DCM-causing genetic variants without the DCM phenotype. We assessed cardiac, obstetric, and fetal or neonatal outcomes in this group of patients. METHODS: We studied 48 women carrying pathogenic or likely pathogenic DCM-associated variants (30 with DCM and 18 without DCM) who had 83 pregnancies. Adverse cardiac events were defined as heart failure (HF), sustained ventricular tachycardia, ventricular assist device implantation, heart transplant, and/or maternal cardiac death during pregnancy, or labor and delivery, and up to the sixth postpartum month. RESULTS: A total of 15 patients, all with DCM (31% of the total cohort and 50% of women with DCM) experienced adverse cardiac events. Obstetric and fetal or neonatal complications were observed in 14% of pregnancies (10 in DCM patients and 2 in genetic carriers). We analyzed the 30 women who had been evaluated before their first pregnancy (12 with overt DCM and 18 without the phenotype). Five of the 12 (42%) women with DCM had adverse cardiac events despite showing NYHA class I or II before pregnancy. Most of these women had a history of cardiac events before pregnancy (80%). Among the 18 women without phenotype, 3 (17%) developed DCM toward the end of pregnancy. CONCLUSIONS: Cardiac complications during pregnancy and postpartum were common in patients with genetic DCM and were primarily related to HF. Despite apparently good tolerance of pregnancy in unaffected genetic carriers, pregnancy may act as a trigger for DCM onset in a subset of these women.

[The importance of genetics in the study of hypertriglyceridemia]. / La importancia de la genética en el estudio de la hipertrigliceridemia.

Hypertriglyceridemia encompasses a set of lipid disorders common in clinical practice, generally defined as a fasting concentration above 150mg/dL. There are various classifications of the severity of hypertriglyceridaemia based on serum values, with levels generally considered moderate when below 500mg/dL and severe when above 1000mg/dL. Its importance lies in its association with other alterations in the lipid profile, contributing to increased cardiovascular risk and increased risk of acute pancreatitis, mainly with concentrations above 500mg/dL.

Factores genéticos asociados a long COVID / Genetic factors associated with long COVID

Introducción: La variabilidad de la expresión y la evolución de la COVID no se explican completamente por los factores clínicos, atribuyéndose un importante papel a los genéticos. Además, se ha planteado si los mismos componentes genéticos que participan en la susceptibilidad y gravedad de la infección influyen en su evolución hacia long COVID. Como objetivo nos propusimos revisar la literatura a fin de conocer cuáles son los factores genéticos que intervienen en la génesis de la COVID persistente. Material y métodos: Revisión sistemática en PubMed y repositorios bioRxiv y medRxiv con base en los descriptores y términos Medical Subject Headings (MeSH) relacionados con COVID y factores genéticos. Fueron seleccionados 2.705 artículos. Un primer cribado, realizado de manera independiente por los autores, redujo la lista a 205 y finalmente, tras un análisis más detallado, se eligieron 85 trabajos para su lectura completa y revisión. Resultados: La enzima convertidora de angiotensina 2 (ACE2) y la proteasa transmembrana, serina 6 (TMPSS6) están implicadas en la susceptibilidad, sin embargo, no se ha encontrado su participación en long COVID. Sí se han hallado algunas asociaciones entre genes, que intervienen en la respuesta inflamatoria e inmune, con la gravedad de la enfermedad y el desarrollo de long COVID. La relación más importante se ha observado en el locus FOXP4. Conclusiones: Aunque actualmente la información sobre long COVID es limitada, parece claro que los factores genéticos identificados hasta ahora no justifican la progresión hacia una enfermedad persistente y se debe considerar la participación de otros componentes como la acción poligénica, de genes pleiotrópicos, de la microbiota y de los cambios epigenéticos.(AU)

Introduction: The variability in expression and evolution of COVID is not completely explained by clinical factors. In fact, genetic factors play an important role. Moreover, it is unknown whether the genetic factor that contribute to susceptibility and severity are also involved in the onset and evolution of long-COVID. The objective of this review is to gather information from literature to understand which genetic factors are involved in the onset of persistent COVID. Material and methods: Systematic review in PubMed and bioRxiv and medRxiv repositories based on MeSH-descriptors and MeSH-terms related to COVID and genetic factors. Using these terms 2715 articles were pooled. An initial screening performed by authors independently, selected 205 articles of interest. A final deeper screening a total of 85 articles were chosen for complete reading and summarized in this review. Results: Although ACE2 and TMPSS6 are involved in COVID susceptibility, their involvement in long-COVID has not been found. On the other hand, the severity of the disease and the onset of long-COVID has been associated with different genes involved in the inflammatory and immune response. Particularly interesting has been the association found with the FOXP4 locus. Conclusions: Although studies on long-COVID are insufficient to fully comprehend the cause, it is clear that the current identified genetic factors do not fully explain the progression and onset of long-COVID. Other factors such as polygenic action, pleiotropic genes, the microbiota and epigenetic changes must be considered and studied.(AU)

Historia natural de la mucopolisacaridosis III en una serie de pacientes colombianos / Natural history of mucopolysaccharidosis type III in a series of Colombian patients

Introducción: La mucopolisacaridosis de tipo III (MPS III), o síndrome de Sanfilippo, es un trastorno de almacenamiento lisosómico con características neurodegenerativas progresivas, predominante del sistema nervioso central. Su diagnóstico se basa en el cuadro clínico, y priman alteraciones en el neurodesarrollo y neuropsiquiátricas, incluso antes de la presencia de alteraciones fenotípicas. El análisis bioquímico para identificar el tipo de glucosaminoglucanos presente, la determinación enzimática y el estudio de genética molecular confirman la enfermedad. Casos clínicos: Se realiza la descripción clínica de ocho pacientes con diagnóstico de MPS III en Colombia, con síntomas iniciales en relación con retraso del desarrollo y trastornos comportamentales evidenciados entre los 3 y 8 años, asociado a facies toscas, cejas pobladas, hepatomegalia y pérdida auditiva progresiva en todos los casos. Uno de los pacientes presentó anomalías cardíacas; dos de ellos, epilepsia focal; y en uno se evidenció atrofia óptica. Todos presentaron alteraciones en las neuroimágenes con evidencia de pérdida del volumen parenquimatoso, atrofia del cuerpo calloso y adelgazamiento cortical; el diagnostico se realizó a través de estudios bioquímicos de cromatografía de glucosaminoglucanos y todos cuentan con un estudio genético confirmatorio. Conclusiones: La MPS III es un desafío diagnóstico, particularmente en pacientes con un curso atenuado de la enfermedad, debido al curso variable, síntomas neuropsiquiátricos tempranos inespecíficos y falta de características somáticas evidentes en comparación con otros tipos de MPS. Cuando se tiene el diagnóstico definitivo, es fundamental brindar atención interdisciplinaria para el paciente y la familia, y apoyar el tratamiento de los síntomas físicos, garantizando ofrecer el mejor cuidado posible y la mejor calidad de vida para el paciente y su familia, al tratarse de una condición neurodegenerativa.(AU)

Introduction: Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a lysosomal storage disease with progressive neurodegenerative features, predominantly affecting the central nervous system. Diagnosis is based on clinical features, with neurodevelopmental and neuropsychiatric alterations taking precedence, including over phenotype alterations. The disease is confirmed by biochemical analysis to identify the type of glycosaminoglycans present, enzyme assay and molecular genetic studies. Case reports: A clinical description was performed for eight patients diagnosed with MPS III in Colombia. Their initial symptoms were related to developmental delay and behavioural disorders presenting between 3 and 8 years of age, associated in all cases with coarse facial features, thick eyebrows, hepatomegaly and progressive hearing loss. One of the patients presented cardiac anomalies; two presented focal epilepsy; and one presented optic atrophy. They all presented neuroimaging alterations, with evidence of parenchymal volume loss, corpus callosum atrophy and cortical thinning; the diagnosis was performed by biochemical glycosaminoglycan chromatography studies, and all patients have a confirmatory genetic study. Conclusions: MPS III is a challenge for diagnosis, particularly in its early stages and in patients in which the course of the disease is attenuated. This is due to its variable course, non-specific early neuropsychiatric symptoms, and the absence of obvious somatic features compared to other types of MPS. After a definitive diagnosis has been made, interdisciplinary care must be provided for the patient and their family, and support given for the treatment of physical symptoms, ensuring the best possible care and quality of life for the patient and their family, as the condition is neurodegenerative.(AU)

A propósito de un caso de síndrome de Fraser. Autopsia de un feto de 37 semanas de gestación con múltiples malformaciones / About a case of Fraser syndrome. Autopsy of a 37 weeks gestation fetus with multiple malformations

El síndrome de Fraser o síndrome criptoftalmos/sindactilia es una enfermedad genética rara, cuyo diagnóstico se basa en una serie de criterios clínicos mayores y menores, y que puede apoyarse en pruebas genéticas. En este artículo se presenta el caso de una autopsia fetal de 37 semanas de gestación con sospecha de síndrome de CHAOS (síndrome obstructivo congénito de las vías aéreas altas). (AU)

Fraser syndrome or cryptophthalmos-syndactyly syndrome is a rare genetic disease, the diagnosis of which is based on a series of major and minor clinical criteria and that can be supported by genetic tests. This article presents the case of a fetal autopsy at 37 weeks of gestation with suspicion of CHAOS syndrome (congenital obstructive syndrome of the upper airways). (AU)

A propósito de un caso de síndrome de Fraser. Autopsia de un feto de 37 semanas de gestación con múltiples malformaciones / About a case of Fraser syndrome. Autopsy of a 37 weeks gestation fetus with multiple malformations

El síndrome de Fraser o síndrome criptoftalmos/sindactilia es una enfermedad genética rara, cuyo diagnóstico se basa en una serie de criterios clínicos mayores y menores, y que puede apoyarse en pruebas genéticas. En este artículo se presenta el caso de una autopsia fetal de 37 semanas de gestación con sospecha de síndrome de CHAOS (síndrome obstructivo congénito de las vías aéreas altas). (AU)

Fraser syndrome or cryptophthalmos-syndactyly syndrome is a rare genetic disease, the diagnosis of which is based on a series of major and minor clinical criteria and that can be supported by genetic tests. This article presents the case of a fetal autopsy at 37 weeks of gestation with suspicion of CHAOS syndrome (congenital obstructive syndrome of the upper airways). (AU)

Exploring the impact of pharmacogenetics on personalized medicine: A systematic review.

INTRODUCTION: Pharmacogenetics evaluates how genetic variations influence drug responses. Nowadays, genetic tests have advanced, becoming more affordable, and its integration is supported by stronger clinical evidence. Guidelines such as those from CPIC (Clinical Pharmacogenetics Implementation Consortium) and resources like PharmGKB facilitate genotype-based prescribing; and organizations like the FDA promote genetic testing before initiating certain medications. Preventive pharmacogenetic panels seem promising, but further research on biomarkers and diverse populations is needed. The aim of this review is to analyze recent evidence on the genotype-drug response relationship to examine how the genetic profile of patients influences the clinical response to treatments, and analyze the areas of research that need further study to advance towards a genetic-based precision medicine. MATERIALS AND METHODS: A systematic search was conducted on PubMed to identify articles investigating the genotype-drug response relationship. The search strategy included terms such as "pharmacogenetics", "personalized treatment", "precision medicine", "dose adjustment", "individualizing dosing", "clinical routine", and "clinical practice." Clinical trials, observational studies, and meta-analyses published in English or Spanish between 2013 and 2023 were included. The initial search resulted in a total of 136 articles for analysis. RESULTS: 49 articles were included for the final analysis following review by 2 investigators. A relationship between genetic polymorphisms and drug response or toxicity was found for drugs such as opioids, GLP-1 agonists, tacrolimus, oral anticoagulants, antineoplastics, atypical antipsychotics, efavirenz, clopidogrel, lamotrigine, anti-TNFα agents, voriconazole, antidepressants, or statins. However, for drugs like metformin, quetiapine, irinotecan, bisoprolol, and anti-VEGF agents, no statistically significant association between genotype and response was found. CONCLUSION: The studies analyzed in this review suggest a strong correlation between genetic variability and individual drug responses, supporting the use of pharmacogenetics for treatment optimization. However, for certain drugs like metformin or quetiapine, the influence of genotype on their response remains unclear. More studies with larger sample sizes, greater ethnic diversity, and consideration of non-genetic factors are needed. The lack of standardization in analysis methods and accessibility to genetic testing are significant challenges in this field. As a conclusion, pharmacogenetics shows immense potential in personalized medicine, but further research is required.

Agregación familiar en el síndrome de colon irritable en pacientes mexicanos. Un estudio de casos y controles / Familial aggregation in Irritable Colon Syndrome in Mexican patients. A case-control study

Objetivo: Determinar la existencia de un patrón familiar de agregación del síndrome de intestino irritable (SII). Diseño: Es un estudio de casos y controles con proporción 1:2, llevado a cabo en una consulta externa de medicina general-familiar. Participantes: Hombres y mujeres de 18 a 60 años. Participaron 40 casos con SII de acuerdo con criterios de Roma IV, y 80 controles integrados por familiares sin alguna enfermedad gastrointestinal. Las mediciones principales fueron variables sociodemográficas, algún evento estresante relacionado, patrón evacuatorio predominante y patrón de repetición familiar para SII. Se analizaron los datos con estadísticas descriptivas e inferenciales. X2 para datos categóricos, estimación de odds ratio (OR) con intervalo de confianza (IC) 95%. Fue aprobado por el comité de ética institucional. Resultados: Hubo repetición del patrón de presentación del SII en familiares principalmente de primer grado. Fue mayor el riesgo de padecer este síndrome cuando el padre lo reportó (OR de 11,2; IC 95% 2-100,1), que cuando la madre lo presentó (OR 3,7; IC 95% 1,4-9,9), o hermano(a) (OR 2,8; IC 95% 1,1-6,6). En ambos grupos, el familiar que más frecuentemente presentaba SII fue en la línea colateral (hermano/a) (37,5% en los casos vs. 17,5% en los controles [p=0,023]). En ambos grupos el género predominante fue el femenino con 80,0% en los casos y 57,5% en los controles. Conclusión: Existe en la población mexicana un patrón de agregación familiar. La enfermedad es más frecuente en familiares en primer grado. Es importante dilucidar si quien desempeña el rol más importante en SII es el trasfondo genético o el entorno familiar.(AU)

Objective: To determine a family aggregation pattern of Irritable Bowel Syndrome (IBS). Design: it is a case-control study with a 1.2 ratio. Setting. External consultation of a general family medicine practice. Participants: men and women from 18 to 60 years old. Cases (40): people with IBS according to the Rome IV criteria, and Controls (80): relatives without gastrointestinal disease. Main measurements. Sociodemographic variables, related stressful events, predominant evacuation patterns, and family repetition patterns for IBS. Data were analyzed with descriptive and inferential statistics. Chi-square for categorical data (< p.05 as significant) estimate of ORs with 95% confidence interval. The institutional ethics committee approved it. Results: The IBS presentation pattern was repeated in relatives, mainly first-degree. The risk of suffering from IBS was higher when the father reported it (OR 11.2 (95% CI; 1.2 -100.1), than the mother OR 3,7 (95% CI; 1.4 – 9.9), sibling OR 2.8 (95% CI; 1.1 – 6.6. In both groups, the relative who most frequently presented IBS was in the collateral line (sibling) (37.5% in cases vs. 17.5% in controls (p=0.023). In both groups, the predominant gender was female, with 80. 0% in cases and 57.5% in controls. Conclusion: SII has a familial recurrence pattern in the Mexican population. The disease is more frequent in first-degree relatives. It is important to elucidate the importance of the role that plays genetic background vs. the influence of the family environment in SII.(AU)

Polimorfismos de los genes CCR5, IL-6, IFN-γ e IL-10 en pacientes cubanos con VIH/sida / Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients

Introducción Los estudios genéticos han demostrado asociaciones de varios polimorfismos de un solo nucleótido (SNP) con diferentes tasas de progresión y variación en la susceptibilidad a la infección por VIH. Este estudio tuvo como objetivo estimar la frecuencia de los polimorfismos ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A e IL-10-1082A/G en pacientes cubanos infectados por VIH y un grupo de parejas serodiscordantes para evaluar su influencia sobre el riesgo y la progresión de la enfermedad. Métodos Se realizó un estudio transversal en 120 sujetos atendidos en el Instituto de Medicina Tropical «Pedro Kour» (IPK) y el Hospital Hermanos Ameijeiras entre junio de 2018 y diciembre de 2019. La amplificación de los fragmentos de los genes ccr5, IL-6, IFN-γ e IL-10 se realizó mediante reacción en cadena de la polimerasa seguida por el análisis del polimorfismo de fragmentos de restricción utilizando la enzima NlaIII para la IL-6. El sistema de mutación refractario a la amplificación por PCR se utilizó en el caso de los genes IFN-γ e IL-10. Resultados Las distribuciones alélicas y genotípicas de los genes ccr5, IL-6, IFN-γ e IL-10 no difirieron significativamente entre los dos grupos. Los recuentos celulares y los valores de carga viral en plasma no difirieron significativamente entre los genotipos de los genes ccr5, IL-6, IFN-γ e IL-10. Solo el genotipo IL-6 GC se asoció con valores más altos de carga viral. La combinación de alelos de los cuatro SNP considerados mostró un aumento muy significativo del riesgo de infección por VIH para uno de ellos, pero con una frecuencia muy baja (<1%). Conclusión Este estudio contribuye a evaluar la frecuencia de estos polimorfismos y su influencia en los biomarcadores de la progresión de la infección por VIH en la población cubana con infección por el VIH. (AU)

Introduction Genetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. Methods A cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour» (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification refractory mutation system was used for IFN-γ and IL-10 genes. Results The allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). Conclusion This study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population. (AU)

Polimorfismos de los genes CCR5, IL-6, IFN-γ e IL-10 en pacientes cubanos con VIH/sida / Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients

Introducción Los estudios genéticos han demostrado asociaciones de varios polimorfismos de un solo nucleótido (SNP) con diferentes tasas de progresión y variación en la susceptibilidad a la infección por VIH. Este estudio tuvo como objetivo estimar la frecuencia de los polimorfismos ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A e IL-10-1082A/G en pacientes cubanos infectados por VIH y un grupo de parejas serodiscordantes para evaluar su influencia sobre el riesgo y la progresión de la enfermedad. Métodos Se realizó un estudio transversal en 120 sujetos atendidos en el Instituto de Medicina Tropical «Pedro Kour» (IPK) y el Hospital Hermanos Ameijeiras entre junio de 2018 y diciembre de 2019. La amplificación de los fragmentos de los genes ccr5, IL-6, IFN-γ e IL-10 se realizó mediante reacción en cadena de la polimerasa seguida por el análisis del polimorfismo de fragmentos de restricción utilizando la enzima NlaIII para la IL-6. El sistema de mutación refractario a la amplificación por PCR se utilizó en el caso de los genes IFN-γ e IL-10. Resultados Las distribuciones alélicas y genotípicas de los genes ccr5, IL-6, IFN-γ e IL-10 no difirieron significativamente entre los dos grupos. Los recuentos celulares y los valores de carga viral en plasma no difirieron significativamente entre los genotipos de los genes ccr5, IL-6, IFN-γ e IL-10. Solo el genotipo IL-6 GC se asoció con valores más altos de carga viral. La combinación de alelos de los cuatro SNP considerados mostró un aumento muy significativo del riesgo de infección por VIH para uno de ellos, pero con una frecuencia muy baja (<1%). Conclusión Este estudio contribuye a evaluar la frecuencia de estos polimorfismos y su influencia en los biomarcadores de la progresión de la infección por VIH en la población cubana con infección por el VIH. (AU)

Introduction Genetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. Methods A cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour» (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification refractory mutation system was used for IFN-γ and IL-10 genes. Results The allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). Conclusion This study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population. (AU)

Transcriptome data from silica-preserved leaf tissue reveal gene flow patterns in a Caribbean bromeliad.

BACKGROUND AND AIMS: Transcriptome sequencing is a cost-effective approach that allows researchers to study a broad range of questions. However, to preserve RNA for transcriptome sequencing, tissue is often kept in special conditions, such as immediate ultracold freezing. Here, we demonstrate that RNA can be obtained from 6-month-old, field-collected samples stored in silica gel at room temperature. Using these transcriptomes, we explore the evolutionary relationships of the genus Pitcairnia (Bromeliaceae) in the Dominican Republic and infer barriers to gene flow. METHODS: We extracted RNA from silica-dried leaf tissue from 19 Pitcairnia individuals collected across the Dominican Republic. We used a series of macro- and micro-evolutionary approaches to examine the relationships and patterns of gene flow among individuals. KEY RESULTS: We produced high-quality transcriptomes from silica-dried material and demonstrated that evolutionary relationships on the island match geography more closely than species delimitation methods. A population genetic examination indicates that a combination of ecological and geographical features presents barriers to gene flow in Pitcairnia. CONCLUSIONS: Transcriptomes can be obtained from silica-preserved tissue. The genetic diversity among Pitcairnia populations does not warrant classification as separate species, but the Dominican Republic contains several barriers to gene flow, notably the Cordillera Central mountain range.

[About a case of Fraser syndrome. Autopsy of a 37 weeks gestation fetus with multiple malformations]. / A propósito de un caso de síndrome de Fraser. Autopsia de un feto de 37 semanas de gestación con múltiples malformaciones.

Fraser syndrome or cryptophthalmos-syndactyly syndrome is a rare genetic disease, the diagnosis of which is based on a series of major and minor clinical criteria and that can be supported by genetic tests. This article presents the case of a fetal autopsy at 37 weeks of gestation with suspicion of CHAOS syndrome (congenital obstructive syndrome of the upper airways).

[Genetic factors associated with long COVID]. / Factores genéticos asociados a long COVID.

INTRODUCTION: The variability in expression and evolution of COVID is not completely explained by clinical factors. In fact, genetic factors play an important role. Moreover, it is unknown whether the genetic factor that contribute to susceptibility and severity are also involved in the onset and evolution of long-COVID. The objective of this review is to gather information from literature to understand which genetic factors are involved in the onset of persistent COVID. MATERIAL AND METHODS: Systematic review in PubMed and bioRxiv and medRxiv repositories based on MeSH-descriptors and MeSH-terms related to COVID and genetic factors. Using these terms 2715 articles were pooled. An initial screening performed by authors independently, selected 205 articles of interest. A final deeper screening a total of 85 articles were chosen for complete reading and summarized in this review. RESULTS: Although ACE2 and TMPSS6 are involved in COVID susceptibility, their involvement in long-COVID has not been found. On the other hand, the severity of the disease and the onset of long-COVID has been associated with different genes involved in the inflammatory and immune response. Particularly interesting has been the association found with the FOXP4 locus. CONCLUSIONS: Although studies on long-COVID are insufficient to fully comprehend the cause, it is clear that the current identified genetic factors do not fully explain the progression and onset of long-COVID. Other factors such as polygenic action, pleiotropic genes, the microbiota and epigenetic changes must be considered and studied.

Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients.

INTRODUCTION: Genetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. METHODS: A cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour¼ (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification Refractory Mutation System was used for IFN-γ and IL-10 genes. RESULTS: The allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). CONCLUSION: This study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population.