RESUMO
OBJECTIVE: The aim of this study was to expand the spectrum of epilepsy syndromes related to STX1B, encoding the presynaptic protein syntaxin-1B, and establish genotype-phenotype correlations by identifying further disease-related variants. METHODS: We used next-generation sequencing in the framework of research projects and diagnostic testing. Clinical data and EEGs were reviewed, including already published cases. To estimate the pathogenicity of the variants, we used established and newly developed in silico prediction tools. RESULTS: We describe 17 new variants in STX1B, which are distributed across the whole gene. We discerned 4 different phenotypic groups across the newly identified and previously published patients (49 patients in 23 families): (1) 6 sporadic patients or families (31 affected individuals) with febrile and afebrile seizures with a benign course, generally good drug response, normal development, and without permanent neurologic deficits; (2) 2 patients with genetic generalized epilepsy without febrile seizures and cognitive deficits; (3) 13 patients or families with intractable seizures, developmental regression after seizure onset and additional neuropsychiatric symptoms; (4) 2 patients with focal epilepsy. More often, we found loss-of-function mutations in benign syndromes, whereas missense variants in the SNARE motif of syntaxin-1B were associated with more severe phenotypes. CONCLUSION: These data expand the genetic and phenotypic spectrum of STX1B-related epilepsies to a diverse range of epilepsies that span the International League Against Epilepsy classification. Variants in STX1B are protean and contribute to many different epilepsy phenotypes, similar to SCN1A, the most important gene associated with fever-associated epilepsies.
Assuntos
Síndromes Epilépticas/genética , Sintaxina 1/genética , Adolescente , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Deficiências do Desenvolvimento , Epilepsia Resistente a Medicamentos/genética , Eletroencefalografia , Epilepsias Parciais/genética , Epilepsias Parciais/fisiopatologia , Síndromes Epilépticas/tratamento farmacológico , Síndromes Epilépticas/fisiopatologia , Síndromes Epilépticas/psicologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Deficiências da Aprendizagem , Mutação com Perda de Função , Masculino , Mutação de Sentido Incorreto , Fenótipo , Convulsões Febris , Análise de Sequência de DNA , Adulto JovemRESUMO
OBJECTIVE: The aim of this pilot study was to compare spirometric values obtained with different types of spirometers, spirometers of same type, and repeated measurements with the same spirometer in a pulmonary function laboratory setting. RESULTS: 12 healthy volunteers performed spirometry on four hot-wire (SensorMedics), two ultrasonic (Spirare) and one wedge-bellows (Vitalograph S) spirometers, according to ATS/ERS (American Thoracic Society/European Respiratory Society) guidelines. Spirometric values were compared using linear mixed models analysis with a random intercept for subjects and a fixed effect for type of spirometer used. Confidence intervals and p values were adjusted for multiple comparisons. Mean ± SD (L) values for hot-wire, ultrasonic and wedge-bellows spirometers for FVC (forced vital capacity) were 4.02 ± 0.66, 3.69 ± 0.61 and 3.93 ± 0.69, and for FEV1 (forced expiratory volume in one second) 3.06 ± 0.44, 2.95 ± 0.44 and 3.10 ± 0.49. Significant differences were found between hot-wire and ultrasonic and between wedge-bellows and ultrasonic spirometers for FVC and FEV1, and between hot-wire and wedge-bellows spirometers for FVC but not for FEV1. There were no significant differences between spirometers of same type, and low mean differences in repeated measurements for all spirometers included. In conclusion, the pilot study shows systematically higher values for FVC and FEV1 for hot-wire and wedge-bellows compared to ultrasonic spirometers.