Relación entre el nivel de heteroplasmia de la mutación m.3243AG en diferentes tejidos y el fenotipo en familias con diabetes y sordera de herencia materna (midd) y melas

El MELAS y la Diabetes y Sordera de Herencia Materna (MIDD) son enfermedades mitocondriales producidas en la mayor parte de los casos por una misma mutación: la m.3243AG, la cual afecta al gen MT-TL1. Esto muestra la gran variabilidad fenotípica de dicha mutación. Una de las posibles causas de esta variación puede ser el nivel de heteroplasmia de la mutación. Este trabajo se propuso evaluar si existe relación entre el nivel de heteroplasmia en tres tejidos y el fenotipo. Fueron incluidas 3 familias con diagnóstico clínico de MELAS y 2 con diagnóstico clínico de MIDD. Se evaluó la presencia de la mutación y el nivel de heteroplasmia mediante ARMS-qPCR EN sangre, orina y mucosa oral. Una familia con MELAS resultó positiva para la mutación m.3243AG. Se evidenció una gran variabilidad fenotípica. El probando tenía una mayor heteroplasmia en los 3 tejidos en comparación con sus familiares oligosintomáticos. Se reporta el primer paciente en Colombia con MELAS y la mutación m.3271TC y se realizó un análisis de estas familiasAbstract. MELAS and Maternally Inherited Diabetes and Deafness (MIDD) are mitochondrial diseases produced in most cases by the same mutation: m.3243AG, which affects the MT-TL1 gene. This reveals the great phenotypic variability of this mutation. One of the possible causes of this could be the mutation´s heteroplasmy level. This project aimed to assess if there is a relation between the heteroplasmy level in three tissues and the phenotype. 3 families with a clinical diagnosis of MELAS and 2 families with a clinical diagnosis of MIDD were included. The presence and heteroplasmy level of the mutation were assessed via ARMS-qPCR on blood, urine and oral mucosa. One family with MELAS rendered positive for the m.3243AG mutation. A great phenotypic variation was found. The proposita had a greater heteroplasmy level in all 3 tissues compared to her oligosymptomatic relatives. The first Colombian patient with MELAS and the m.3271TC mutation is reported. These families were further analyzed.Maestrí

PTPN4 germline variants result in aberrant neurodevelopment and growth

Protein-tyrosine phosphatases (PTPs) are pleomorphic regulators of eukaryotic cellular responses to extracellular signals that function by modulating the phosphotyrosine of specific proteins. A handful of PTPs have been implicated in germline and somatic human disease. Using exome sequencing, we identified missense and truncating variants i

Creación de una empresa dedicada a la producción y comercialización de ajiáco congelado de fácil y rápida preparación en la ciudad de Bogotá D.C.

La producción y comercialización de las ajiacos congelados bajo la razón social de INSTASOPAS S.A.S., se encuentra ubicada en la ciudad de Bogotá, más específicamente en la localidad de Santa Fe, en la Carrera 14 bis No. 21-35 sector de San Victorino, buscando ofrecer a los restaurantes en la ciudad de Bogotá un producto proveniente de materias primas naturales, brindando una excelente calidad en cuanto a sabor y duración, teniendo en cuenta a su vez la practicidad del producto a la hora de ser preparado para la venta a los diferentes clientes que responden a las necesidades de nuestro producto. Sometido el ajiaco a un proceso de pre cocción con sus respectivos ingredientes, se procede a ser congelado el producto para su almacenamiento y posterior distribución de manera independiente para cada uno de los diferentes restaurantes interesados en el producto. La intención del mercado objetivo de INSTASOPAS S.A.S. es que se perciba el producto como cercano y familiar, sintiendo confianza en la empresa y en el producto como un gran aliado en la prestación de un adecuado servicio y ofrecimiento de un producto confiable para el consumidor para obtener los mejores resultados generando ahorro en tiempo de preparación para los restaurantes hacia sus clientes, y a su vez aumentando la capacidad de atención de clientes brindando un servicio de mejor calidad.Ingeniero (a) IndustrialPregrad

Infantile-onset Pompe disease complicated by sickle cell anemia: Case report and management considerations

Infantile-onset Pompe disease (IOPD) is a rare, severe disorder of lysosomal storage of glycogen that leads to progressive cardiac and skeletal myopathy. IOPD is a fatal disease in childhood unless treated with enzyme replacement therapy (ERT) from an early age. Sickle cell anemia (SCA) is a relatively common hemoglobinopathy caused by a specific variant in the hemoglobin beta-chain. Here we report a case of a male newborn of African ancestry diagnosed and treated for IOPD and SCA. Molecular testing confirmed tw

Case studies of two families with MIDD and MELAS: heteroplasmy level in m.3243A>G mutation and the first report on m.3271T>C mutation in Colombia

El síndrome MELAS (encefalomiopatía mitocondrial, acidosis láctica y episodios similares a isquemia cerebral) y el síndrome MIDD (diabetes y sordera de herencia materna) son enfermedades mitocondriales producidas en la mayor parte de los casos por una misma mutación: la m.3243A>G que afecta al gen MT-TL1. Se presentan los casos de dos familias con MELAS. En la primera se detecta la mutación m.3243A>G y se determina el nivel de heteroplasmia en sangre, orina y mucosa oral, con lo que se evidencia una gran variabilidad fenotípica: la paciente tenía una mayor heteroplasmia en los tres tejidos en comparación con sus familiares oligosintomáticos y la madre tenía una glicemia elevada e hipoacusia, sugiriendo un fenotipo cercano al MIDD. En la segunda familia se detecta la mutación m.3271T>C, siendo el primer caso reportado en Colombia. Estos hallazgos sugieren que el MIDD y el MELAS, descritos frecuentemente como entidades distintas, hacen parte de una misma entidad con expresividad variable dependiendo en parte de la heteroplasmia.MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) and MIDD syndrome (maternally inherited diabetes and deafness) are mitochondrial diseases caused in most cases by the same mutation m.3243A> G, which affects the gene MT-TL1. The cases of two families with MELAS are presented here. In the first case, the m.3243A>G mutation was detected and the heteroplasmy level in blood, urine and oral mucosa were determined, finding a great phenotypic variability: the patient had higher heteroplasmy in the three tissues compared against oligosymptomatic relatives, and the mother had high blood sugar levels and hearing loss, suggesting a phenotype near to MIDD. In the second family, the m.3271T>C mutation was detected, which constitutes the first case reported in Colombia. These findings suggest that MIDD and MELAS, often described as distinct entities, are part of the same entity with variable expressivity partially depending on heteroplasmy

Case studies of two families with MIDD and MELAS: heteroplasmy level in m.3243A>G mutation and the first report on m.3271T>C mutation in Colombia

MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) and MIDD syndrome (maternally inherited diabetes and deafness) are mitochondrial diseases caused in most cases by the same mutation m.3243A> G, which affects the gene MT-TL1. The cases of two families with MELAS are presented here. In the first case, the m.3243A>G mutation was detected and the heteroplasmy level in blood, urine and oral mucosa were determined, finding a great phenotypic variability: the patient had higher heteroplasmy in the three tissues compared against oligosymptomatic relatives, and the mother had high blood sugar levels and hearing loss, suggesting a phenotype near to MIDD. In the second family, the m.3271T>C mutation was detected, which constitutes the first case reported in Colombia. These findings suggest that MIDD and MELAS, often described as distinct entities, are part of the same entity with variable expressivity partially depending on heteroplasmy

PTPN4 germline variants result in aberrant neurodevelopment and growth

Protein-tyrosine phosphatases (PTPs) are pleomorphic regulators of eukaryotic cellular responses to extracellular signals that function by modulating the phosphotyrosine of specific proteins. A handful of PTPs have been implicated in germline and somatic human disease. Using exome sequencing, we identified missense and truncating variants i

Pathogenic variants in TNRC6B cause a genetic disorder characterised by developmental delay/intellectual disability and a spectrum of neurobehavioural phenotypes including autism and ADHD

BACKGROUND: Rare variants in hundreds of genes have been implicated in developmental delay (DD), intellectual disability (ID) and neurobehavioural phenotypes. METHODS: Clinical and molecular characterisation was performed on 17 patients with TNRC6B variants. Clinical data were obtained by retrospective chart review, parent interviews, direct patient interaction with providers and formal neuropsychological evaluation. RESULTS: Clinical findings included DD/ID (17/17) (speech delay in 94% (16/17), fine motor delay in 82% (14/17) and gross motor delay in 71% (12/17) of subjects), autism or autistic traits (13/17), attention deficit and hyperactivity disorder (ADHD) (11/17), other behavioural problems (7/17) and musculoskeletal findings (12/17). Other congenital malformations or clinical findings were occasionally documented. The majority of patients exhibited some dysmorphic features but no recognisable gestalt was identified. 17 heterozygous TNRC6B variants were identified in 12 male and five female unrelated subjects by exome sequencing (14), a targeted panel (2) and a chromosomal microarray (1). The variants were nonsense (7), frameshift (5), splice site (2), intragenic deletions (2) and missense (1). CONCLUSIONS: Variants in TNRC6B cause a novel genetic disorder characterised by recurrent neurocognitive and behavioural phenotypes featuring DD/ID, autism, ADHD and other behavioural abnormalities. Our data highly suggest that haploinsufficiency is the most likely pathogenic mechanism. TNRC6B should be added to the growing list of genes of the RNA-induced silencing complex associated with ID/DD, autism and ADHD