ABSTRACT
BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a rare congenital disorder characterized by broad thumbs and halluces, intellectual disability, distinctive facial features, and growth retardation. Clinical manifestations of RSTS are varied and overlap with other syndromes' phenotype, which makes clinical diagnosis challenging. CREBBP is the major causative gene (55%-60% of the cases), whereas pathogenic variants found in EP300 represent the molecular cause in 8% of RSTS patients. A wide range of CREBBP pathogenic variants have been reported so far, including point mutations (30%-50%) and large deletions (10%). METHODS: The aim of this study was to characterize the CREBBP genetic variant spectrum in 39 RSTS patients using Multiplex Ligation-dependent Probe Amplification and DNA sequencing techniques (Sanger and Trio-based whole-exome sequencing). RESULTS: We identified 15 intragenic deletions/duplications, ranging from one exon to the entire gene. As a whole, 25 de novo point variants were detected: 4 missense, 12 nonsense, 5 frameshift, and 4 splicing pathogenic variants. Three of them were classified as of uncertain significance and one of the patients carried two different variants. CONCLUSION: Seventeen of the 40 genetic variants detected were reported for the first time in this work contributing, thus, to expand the molecular knowledge of this complex disorder.
Subject(s)
CREB-Binding Protein/genetics , E1A-Associated p300 Protein/genetics , Genetic Association Studies , Mutation , Rubinstein-Taybi Syndrome/genetics , Rubinstein-Taybi Syndrome/pathology , Adolescent , Adult , Child , Child, Preschool , Female , Genotype , Humans , Infant , Male , Phenotype , Young AdultSubject(s)
Antibodies, Monoclonal/therapeutic use , Autoimmune Diseases/chemically induced , Autoimmune Diseases/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Muscular Diseases/chemically induced , Muscular Diseases/drug therapy , Proprotein Convertase 9/immunology , Aged , Autoimmune Diseases/immunology , Humans , Hypercholesterolemia/drug therapy , Male , Middle Aged , Muscle Weakness/chemically induced , Muscle Weakness/drug therapy , Muscle Weakness/immunology , Muscular Diseases/immunologyABSTRACT
No disponible
Subject(s)
Humans , Genetic Association Studies , Genetics, Medical/trends , Genetic Markers , Genetic Predisposition to DiseaseABSTRACT
Acute respiratory distress syndrome is a well-known complication in Plasmodium falciparum infection. It is less frequently described in Plasmodium vivax, and only one case is reported in Plasmodium ovale. Here we present the second description of this pulmonary complication in a P. ovale acute infection.
