Resumo: as fissuras labiopalatais são malformações congénitas do sistema estomatognático, ocorrem por alterado das estruturas anatómicas do crânio, face e cavidade oral, por falha na fusão dos tecidos na embriogênese; as malformações podem ser do lábio, palato duro, palato mole, mucosa palatina e, em alguns casos, da cavidade nasal; caso contrário, afetam as estruturas envolvidas nas funções da linguagem, fala e audição. Objetivo: Identificar os fatores genéticos e ambientais associados á fissura labiopalatal. Metodologia: a revisão bibliográfica foi realizada nas bases de dados académicas PubMed, LILACS, OVID-MEDLINE utilizando linguagem normalizada com termos DECS-LILACS: exposição a riscos ambientais, fenda palatina, lábio leporino, genética, medicina de precisão e síndrome; foram aplicados filtros de busca das bases de dados, tipos de textos científicos e informados relevantes para a pesquisa. Segundo os resultados a partir da pesquisa bibliográfica, foi constatado que a etiologia das fissuras é multifatorial e está associada a fatores genéticos e ambientais. A identificado de vários genes relacionados a essas malformações permitiu reconhecer em curto tempo quando urna fissura é sindrómica ou não sindrômica, o que leva ao entendimento da interação gene a gene, identificado de variantes funcionais e compreensão de sua importância etiológica. Conclusóes: o estudo e conhecimento sobre os mecanismos moleculares encontrados envolvidos na formação da fissura labiopalatal ganhou força graças á compreensão do genoma humano e o desenvolvimento de ferramentas modernas de biologia molecular que permitem a identificado de grandes quantidades de dados de sequênces, fazendo com que os genes candidatos aumentem constantemente. Isso permitirá a gestão atempada da doença, identificado do risco de ocorrência e tratamento especializado através da medicina de precisão.

Abstract: cleft lip and palate are congenital malformations of the stomatognathic system; they occur due to an alteration of the anatomical structures of the skull, face and oral cavity, due to a failure in the fusion of tissues in embryogenesis; malformations can be of the lip, hard palate, soft palate, palatal mucosa, and in some cases of the nasal cavity; moreover, they affect the structures involved in the functions of language, speech, and hearing. Objective: To identify the genetic and environmental factors associated with cleft lip and palate. Methodology: the bibliographic review was carried out in PubMed, LILACS, OVID-MEDLINE academic databases using standardized language with decs-lilacs terms: exposure to environmental risks, cleft palate, cleft lip, genetics, precision medicine and syndrome; Search filters of the databases, types of scientific texts and information relevant to the research were applied. According to the results of the bibliographic search, it was found that the etiology of the fissures is multifactorial and is associated with genetic and environmental factors. The identification of various genes related to these malformations has made it possible to timely recognize when a cleft is syndromic or non-syndromic, which leads to understanding gene-by-gene interaction, identifying functional variants and understanding their etiological importance. Conclusions: the study and knowledge regarding the molecular mechanisms that are involved in the formation of cleft lip and palate has gained strength thanks to the understanding of the human genome and the development of modern molecular biology tools that allow the identification of large amounts of sequence data, causing the candidate genes to increase constantly.

Resumen: las fisuras labiopalatinas son malformaciones congénitas del sistema estomatognático, se presentan por alteración de las estructuras anatómicas del cráneo, la cara y la cavidad bucal, debido a una falla en la fusión de tejidos en la embriogénesis; las malformaciones pueden ser del labio, el paladar duro, el velo del paladar, la mucosa palatina y en algunos casos de la cavidad nasal; por lo demás, afectan las estructuras que participan en las funciones del lenguaje, el habla y la audición. Objetivo: Identificar los factores genéticos y ambientales asociados a las fisuras labiopalatinas. Metodología: la revisión bibliográfica se realizó en bases de datos académicas PubMed, LILACS, OVID-MEDLINE usando lenguaje normalizado con términos DECS-LILACS: exposición a riesgos ambientales, fisura del paladar, labio leporino, genética, medicina de precisión y síndrome; se aplicaron filtros de búsqueda propios de las bases de datos, tipos de textos científicos e información relevante para la investigación. De acuerdo con los resultados de la búsqueda bibliográfica se encontró que la etiología de las fisuras es multifactorial y se asocia a factores genéticos y ambientales. La identificación de diversos genes relacionados con estas malformaciones ha permitido reconocer oportunamente cuándo una fisura es sindrómica o no sindrómica, lo que lleva a entender la interacción gen por gen, a identificar variantes funcionales y a comprender su importancia etiológica. Conclusiones: el estudio y el conocimiento acerca de los mecanismos moleculares que se encuentran involucrados en la formación de las fisuras labiopalatinas ha tomado fuerza gracias al entendimiento del genoma humano y al desarrollo de herramientas modernas de biología molecular que permiten identificar gran cantidad de datos de secuencia, haciendo que los genes candidatos aumenten constantemente. Esto permitirá un manejo oportuno de la enfermedad, la identificación del riesgo de ocurrencia y un tratamiento especializado mediante la medicina de precisión.

Abstract Introduction Gaucher's disease (GD) is an autosomal-recessive lysosomal storage disorder that results from hereditary deficiency of the acid glucocerebrosidase enzyme, encoded by the GBA gene necessary for the degradation of glucosylceramide. Objective molecularly characterize the variants found in the GBA gene present in patients from the Southwest of Colombia with GD. Material and methods 19 patients were included in the study, clinically and enzymatically diagnosed with GD. A molecular analysis of the GBA gene was performed and the variants were subsequently searched in different population and clinical databases. A bioinformatic analysis was performed. Results The variants in the GBA gene reported were classified into: 14/19 homozygous patients, 4/19 compound heterozygote and 1/19 heterozygous. The presence of 7 variants coding for 8 different genotypes was reported. Also the known mutations like Asn409Ser, p.Leu483Pro, p.Lys237Glu, p.Glu427Lys, and p.Arg535His were identified in these patients. The most frequent genotype was p. Asn409Ser / Asn409Ser (36%). All the variants presented a pathogenic clinical significance. Conclusion The given study will make it possible to understand the susceptibility to GD in the population. This can help maintain the health quotient of the population through premarital counseling and therefore minimize the burden of disease among the population.

Abstract: Introduction: Camurati-Engelmann disease is an autosomal dominant sclerosing bone dysplasia, estimated at 1:1,000,000 people, with approximately 300 cases reported worldwide. Mutations in TGFB1 gene have been associated with the development of the disease. The objective is to describe clinically and molecularly a Colombian infant with this disease. Clinical case: 22-month-old female patient, daughter of the first pregnancy of non-consanguineous parents, with no family history of diseases. The clinical picture consisted of limb weakness, signs of compromise of the osteo-arthro-neuromuscular system, hence, bone dysplasia was suspected. Molecular study by complete exome sequencing and genomic-bioinformatics study, using in-silico technology, was performed. A missense mutation (c.466C> T; p.Arg156Cys) was found in the TGFB1 gene; by bioinformatics, it was determined that this genetic variant had pathogenic clinical significance. Conclusion: This case provides data from the Camurati-Engelmann disease, highlighting the importance of genomic and bioinformatics techniques for its diagnosis.

Resumen: Introducción: La enfermedad de Camurati-Engelmann es una displasia ósea esclerosante autosómica dominante, se estima en 1:1,000,000 de personas, con aproximadamente 300 casos reportados en el mundo. Las mutaciones en el gen TGFB1 se han asociado con el desarrollo de la enfermedad. El objetivo es describir clínica y molecularmente a una lactante colombiana con la enfermedad. Caso clínico: Paciente femenino de 22 meses, producto del primer embarazo de padres no consanguíneos sin historia familiar de enfermedades, con cuadro clínico de debilidad en extremidades, signos de compromiso de sistema osteo-artro-neuromuscular, sospechando displasia ósea. Se realizó estudio molecular mediante secuenciación de exoma completo y estudio genómico-bioinformático utilizando tecnología in-silico, encontrando una mutación missense (c.466C>T;p.Arg156Cys) en el gen TGFB1; por bioinformática se determinó que esta variante genética tenía significado clínico patogénico. Conclusión: Este caso proporciona datos actualizados de la enfermedad de Camurati-Engelmann, resaltando la importancia de las técnicas genómicas y bioinformáticas para el diagnóstico.

Resumen Introducción. El virus de Epstein-Barr (EBV) es un virus ubicuo y oncogénico, asociado con el desarrollo de enfermedades como la mononucleosis infecciosa, el linfoma de Burkitt, el carcinoma nasofaríngeo y otras neoplasias. Actualmente, se reconocen dos subtipos: EBV-1 y EBV- 2, que tienen diferencias genéticas con sus antígenos nucleares (Epstein-Barr Nuclear Antigens, EBNA). Debido a la gran heterogeneidad y variabilidad encontradas en la proteína LMP1 del virus, se han descrito variantes asociadas con ciertas enfermedades o con regiones geográficas específicas. Objetivo. Identificar y caracterizar molecularmente las variantes del EBV detectadas en la cavidad oral de 84 adolescentes de Cali, Colombia. Materiales y métodos. Se hizo la amplificación por reacción en cadena de la polimerasa (Polymerase Chain Reaction, PCR) convencional, así como la purificación y la secuenciación del gen EBNA3C se realizó para subtipificar el virus y del dominio C-ter de la proteína LMP1 para identificar variantes. Además, se llevó a cabo un análisis filogenético y de variantes nucleotídicas de las secuencias obtenidas comparadas con variantes patogénicas y geográficas reportadas en el GenBank (National Center for Biotechnology Information, NCBI). Resultados. El subtipo viral predominante fue el EBV-1 (79 %); el 72,6 % se agrupó con la variante patogénica Raji, derivada de linfocitos B de un paciente con linfoma de Burkitt; el 13,7 % se relacionó con una variante de origen geográfico del Mediterráneo y otro 13,7 % no se agrupó con ninguna de las variantes de referencia. Conclusiones. Este es el primer estudio que reporta variantes del gen LMP1-EBV en Cali, Colombia. Se requieren nuevos estudios para caracterizar la variante sin identificar y determinar si es patogénica o si es una variante geográfica presente exclusivamente en la ciudad.

Abstract Introduction: The Epstein-Barr virus (EBV) is an ubiquitous and oncogenic virus associated with the development of diseases such as infectious mononucleosis, Burkitt’s lymphoma, nasopharyngeal carcinoma, and other neoplasms. Currently, two types are recognized: EBV-1 and EBV-2, which have genetic differences with their EBNA nuclear antigens. Likewise, due to the high degree of heterogeneity and variability found in the LMP1 protein of the virus, variants associated with pathogenesis or specific geographic regions have been described. Objective: To identify and characterize molecularly EBV variants detected in the oral cavity of 84 adolescents in Cali, Colombia. Materials and methods: Conventional PCR amplification, purification, and sequencing of the gen EBNA3C were carried out to typify the virus and the C-ter domain of the LMP1 protein to identify variants. We also conducted a phylogenetic and nucleotide variant analysis of the obtained sequences versus pathogenic or geographic variants reported in GenBank-NCBI. Results: The predominant viral subtype was EBV-1 (79%); 72.6% was grouped with the pathogenic variant Raji, derived from B lymphocytes of a patient with Burkitt›s lymphoma, 13.7% was related to a variant of Mediterranean origin, and 13.7% was not grouped with any of the reference variants. Conclusions: This is the first time that variants of LMP1-EBV have been identified in Cali, Colombia. Additional studies are necessary to characterize the unidentified variant and to determine if it is pathogenic or if it is just an isolate present in the city of Cali.

ABSTRACT Mucopolysaccharidosis is characterized by excessive accumulation of glycosaminoglycan sulfate in organs and tissues. Otorhinolaryngological and upper respiratory tract pathologies are among the earliest clinical manifestations. We realized a retrospective study of clinical and otorhinolaryngologic findings of 35 patients diagnosed with MPS type II, IV-A and VI of the Colombian southwest. As a result, we found that 64% of the patients evaluated had hearing loss, 11.3% had hypertrophy of the tonsils,17.10% short neck and macroglossia. Additionally, 47.8% of the patients presented otitis media. 20% received treatment with hearing aids. no patient reported otosclerosis or tinittus. In patients with different types of MPS, there is a high frequency and progressive tendency to suffer audiological losses and recurrent infections, so it is important an opportune diagnosis, permanent monitoring and adequate therapy to avoid the repercussion of the pathology in the quality of life of patients.

Resumen: El estudio del cromosoma 2 en los seres humanos ha permitido reconocer que su alteración, basada en una localización específica, puede conducir a diversas enfermedades asociadas. Mediante la identificación fenotípica, sustentada en el estudio molecular de hibridación genómica comparativa y un estudio bioinformático posterior, se detectó la presencia de una duplicación patogénica en la región cromosómica 2p25.3p24.3, relacionada con la afección de 36 genes. Adicionalmente, se identificó una deleción patogénica en la citobanda 2q37.3, relacionada con la afección de 36 genes. El análisis bioinformático demostró interacciones entre genes que explican características sintomatológicas. Esta es la primera vez que se presentan estas dos variantes en un mismo individuo. Ambas alteraciones se han asociado con retraso psicomotor moderado, autismo, neurohipófisis ectópica, aracnodactilia, cardiopatía congénita y alteraciones cardiovasculares. Se ha propuesto que la mutación HDAC4 es la causante de la mayoría de las características del síndrome de microdeleción 2q37. El fenotipo clínico heterogéneo es el resultado del reordenamiento cromosómico encontrado, lo cual permite describir, interpretar y dar un tratamiento oportuno y dirigido a la paciente y la respectiva conserjería genética familiar. Finalmente, esta es la primera vez que se reporta este tipo específico de reordenamiento cromosómico.

Abstract: The study of chromosome 2 in humans has allowed recognizing that its alteration, based on a specific location, can lead to various associated diseases. Through the phenotypic identification, supported by comparative genomic hybridization and subsequent bioinformatic analysis, the presence of a pathogenic duplication was detected in the chromosomal region 2p25.3p24.3 affecting 36 genes. Additionally, a pathogenic deletion was identified in cytoband 2q37.3 affecting 36 genes. The bioinformatic analysis showed interactions among genes that explain symptomatic characteristics. This is the first time that these two variants are present in the same individual. Both disorders have been associated with moderate psychomotor retardation, autism, ectopic neurohypophysis, arachnodactyly, congenital heart disease, and cardiovascular disorders. The hdac4 mutation has been suggested to cause most of the features of 2q37 microdeletion syndrome. The heterogeneous clinical phenotype derives from the chromosomal rearrangement found, which allows describing, interpreting, and providing the patient with timely targeted treatment and the respective family genetic counseling. Finally, this specific type of chromosomal rearrangement has been reported for the first time.

Resumo: O estudo do cromossomo 2 em seres humanos nos permitiu reconhecer que sua alteração, com base em uma localização específica, pode levar a diversas doenças associadas. Por meio da identificação fenotípica, apoiada no estudo molecular da hibridação genômica comparativa e em um estudo bioinformático posterior, foi detectada a presença de uma duplicação patogénica na região cromossômica 2p25.3p24.3, relacionada a 36 genes afetados. Além disso, uma deleção patogénica foi identificada na citobanda 2q37.3, relacionada a 36 genes afetados. A análise bioinformática mostrou interações entre genes que explicam características sintomáticas. É a primeira vez que essas duas variantes são apresentadas no mesmo indivíduo. Ambos os distúrbios tém sido associados a retardo psicomotor moderado, autismo, neuro-hipófise ectópica, aracnodactilia, doenças cardíacas congénitas e distúrbios cardiovasculares. Propõe-se que a mutação hdac4 é a causa da maioria das características da síndrome de microdeleção 2q37. O fenótipo clínico heterogéneo é o resultado do rearranjo cromossômico encontrado, que permite descrever, interpretar e oferecer um tratamento oportuno direcionado ao paciente e ao respectivo aconselhamento genético familiar. Finalmente, também é a primeira vez que esse tipo específico de rearranjo cromossômico é relatado.