RESUMO
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.
Assuntos
Proteína de Ligação a CREB/genética , Proteína p300 Associada a E1A/genética , Estudos de Associação Genética , Mutação , Síndrome de Rubinstein-Taybi/genética , Síndrome de Rubinstein-Taybi/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Masculino , Fenótipo , Adulto JovemAssuntos
Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doenças Musculares/induzido quimicamente , Doenças Musculares/tratamento farmacológico , Pró-Proteína Convertase 9/imunologia , Idoso , Doenças Autoimunes/imunologia , Humanos , Hipercolesterolemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/induzido quimicamente , Debilidade Muscular/tratamento farmacológico , Debilidade Muscular/imunologia , Doenças Musculares/imunologiaRESUMO
No disponible
Assuntos
Humanos , Estudos de Associação Genética , Genética Médica/tendências , Marcadores Genéticos , Predisposição Genética para DoençaRESUMO
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.
