9 research outputs found
Relaci贸n entre el nivel de heteroplasmia de la mutaci贸n 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 mutaci贸n: la m.3243AG, la cual afecta al gen MT-TL1. Esto muestra la gran variabilidad fenot铆pica de dicha mutaci贸n. Una de las posibles causas de esta variaci贸n puede ser el nivel de heteroplasmia de la mutaci贸n. Este trabajo se propuso evaluar si existe relaci贸n entre el nivel de heteroplasmia en tres tejidos y el fenotipo. Fueron incluidas 3 familias con diagn贸stico cl铆nico de MELAS y 2 con diagn贸stico cl铆nico de MIDD. Se evalu贸 la presencia de la mutaci贸n y el nivel de heteroplasmia mediante ARMS-qPCR EN sangre, orina y mucosa oral. Una familia con MELAS result贸 positiva para la mutaci贸n m.3243AG. Se evidenci贸 una gran variabilidad fenot铆pica. El probando ten铆a una mayor heteroplasmia en los 3 tejidos en comparaci贸n con sus familiares oligosintom谩ticos. Se reporta el primer paciente en Colombia con MELAS y la mutaci贸n m.3271TC y se realiz贸 un an谩lisis 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麓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.Maestr铆
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
Creaci贸n de una empresa dedicada a la producci贸n y comercializaci贸n de aji谩co congelado de f谩cil y r谩pida preparaci贸n en la ciudad de Bogot谩 D.C.
La producci贸n y comercializaci贸n de las ajiacos congelados bajo la raz贸n social de INSTASOPAS S.A.S., se encuentra ubicada en la ciudad de Bogot谩, m谩s espec铆ficamente 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 Bogot谩 un producto proveniente de materias primas naturales, brindando una excelente calidad en cuanto a sabor y duraci贸n, 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 cocci贸n con sus respectivos ingredientes, se procede a ser congelado el producto para su almacenamiento y posterior distribuci贸n de manera independiente para cada uno de los diferentes restaurantes interesados en el producto. La intenci贸n 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 prestaci贸n de un adecuado servicio y ofrecimiento de un producto confiable para el consumidor para obtener los mejores resultados generando ahorro en tiempo de preparaci贸n para los restaurantes hacia sus clientes, y a su vez aumentando la capacidad de atenci贸n 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 s铆ndrome MELAS (encefalomiopat铆a mitocondrial, acidosis l谩ctica y episodios similares a isquemia cerebral) y el s铆ndrome MIDD (diabetes y sordera de herencia materna) son enfermedades mitocondriales producidas en la mayor parte de los casos por una misma mutaci贸n: 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 mutaci贸n m.3243A>G y se determina el nivel de heteroplasmia en sangre, orina y mucosa oral, con lo que se evidencia una gran variabilidad fenot铆pica: la paciente ten铆a una mayor heteroplasmia en los tres tejidos en comparaci贸n con sus familiares oligosintom谩ticos y la madre ten铆a una glicemia elevada e hipoacusia, sugiriendo un fenotipo cercano al MIDD. En la segunda familia se detecta la mutaci贸n 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
Pathogenic variants in TNRC6B cause a genetic disorder characterised by developmental delay/intellectual disability and a spectrum of neurobehavioural phenotypes including autism and ADHD
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