14 documents found, page 1 of 2

Análise genómica no Serviço Nacional de Saúde: modelo colaborativo INSA–ULSSM p...

Genetic modulation of RNA splicing rescues BRCA2 function in mutant cells

Variants in the hereditary cancer-associated BRCA1 and BRCA2 genes can alter RNA splicing, producing transcripts that encode internally truncated yet potentially functional proteins. However, few studies have quantitatively analyzed variant-specific splicing isoforms. Here, we investigated cells heterozygous and homozygous for the BRCA2:c.681+5G>C variant. Using droplet digital RT-PCR, we identified two variant...

The added value of a multidisciplinary clinic for systemic autoinflammatory dis...

Background: Systemic autoinflammatory diseases (SAID) are characterized by inappropriate activation of the innate immune system and include not only monogenic periodic fever syndromes but also multifactorial conditions. As SAID are rare and represent a diagnostic challenge, a multidisciplinary approach is important to ensure successful diagnosis and adequate follow-up of these patients. Objective: To describe t...

Bi-allelic variants in the ER quality-control mannosidase gene EDEM3 cause a co...

EDEM3 encodes a protein that converts Man8GlcNAc2 isomer B to Man7-5GlcNAc2. It is involved in the endoplasmic reticulum-associated degradation pathway, responsible for the recognition of misfolded proteins that will be targeted and translocated to the cytosol and degraded by the proteasome. In this study, through a combination of exome sequencing and gene matching, we have identified seven independent families...

AutoMap is a high performance homozygosity mapping tool using next-generation s...

Homozygosity mapping is a powerful method for identifying mutations in patients with recessive conditions, especially in consanguineous families or isolated populations. Historically, it has been used in conjunction with genotypes from highly polymorphic markers, such as DNA microsatellites or common SNPs. Traditional software performs rather poorly with data from Whole Exome Sequencing (WES) and Whole Genome S...

Epileptic Encephalopathies of Childhood: The New Paradigm of Genetic Diagnosis

Introduction: Epileptic encephalopathies of childhood are characterized by early seizure-onset and adverse neurological outcomes. The development of new genetic techniques has allowed an exponential identification of the genes that are involved. Over the last years, we have observed a revolution in the diagnostic paradigm. However, there are no international guidelines regarding the diagnosis of genetic epilept...

GATAD2B-associated neurodevelopmental disorder (GAND) : clinical and molecular ...

Purpose: Determination of genotypic/phenotypic features of GATAD2B-associated neurodevelopmental disorder (GAND). Methods: Fifty GAND subjects were evaluated to determine consistent genotypic/phenotypic features. Immunoprecipitation assays utilizing in vitro transcription-translation products were used to evaluate GATAD2B missense variants' ability to interact with binding partners within the nucleosome remodel...

Koolen-de Vries syndrome – National Case Series with clinical and molecular cha...

Introduction: Koolen-de Vries Syndrome (KdVS) is a rare genetic condition, caused by a 17q21.31 microdeletion, or a pathogenic variant in KANSL1 gene. The clinical picture includes developmental delay (DD)/intellectual disability (ID) with expressive language particularly impaired, dysmorphisms, neonatal hypotonia, and friendly behaviour. Aim: To characterize at the molecular and clinical levels all patients in...

Monozygotic twins concordant for common variable immunodeficiency : strikingly ...

Monozygotic twins provide a unique opportunity to better understand complex genetic diseases and the relative contribution of heritable factors in shaping the immune system throughout life. Common Variable Immunodeficiency Disorders (CVID) are primary antibody defects displaying wide phenotypic and genetic heterogeneity, with monogenic transmission accounting for only a minority of the cases. Here, we report a ...

Ectima Gangrenoso: Um Alerta Para Imunodeficiência

As infeções graves, atípicas, recorrentes ou por agentes oportunistas devem ser sempre um sinal de alerta para imunodeficiência primária. Apresenta-se o caso clínico de uma lactente de 8 meses, previamente saudável, internada por sépsis e lesão na região lombosagrada com necrose central e bordos inflamatórios, sugestiva de ectima gangrenoso. Analiticamente apresentava anemia, neutropenia e proteína C reativa el...