RESUMO
Genetic epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant disorder with febrile or afebrile seizures that exhibits phenotypic variability. Only a few variants in SCN1A have been previously characterized for GEFS+, in Latin American populations where studies on the genetic and phenotypic spectrum of GEFS+ are scarce. We evaluated members in two multi-generational Colombian Paisa families whose affected members present with classic GEFS+. Exome and Sanger sequencing were used to detect the causal variants in these families. In each of these families, we identified variants in SCN1A causing GEFS+ with incomplete penetrance. In Family 047, we identified a heterozygous variant (c.3530C > G; p.(Pro1177Arg)) that segregates with GEFS+ in 15 affected individuals. In Family 167, we identified a previously unreported variant (c.725A > G; p.(Gln242Arg)) that segregates with the disease in a family with four affected members. Both variants are located in a cytoplasmic loop region in SCN1A and based on our findings the variants are classified as pathogenic and likely pathogenic, respectively. Our results expand the genotypic and phenotypic spectrum associated with SCN1A variants and will aid in improving molecular diagnostics and counseling in Latin American and other populations.
Assuntos
Epilepsia , Convulsões Febris , Colômbia , Humanos , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Linhagem , Convulsões Febris/complicações , Convulsões Febris/genéticaRESUMO
INTRODUCTION: Psoriasis is a chronic inflammatory dermatosis, a with variable clinical presentation and whose multifactorial etiology carries an essential genetic component. Multiple genetic variations associated with psoriasis have been described around the world. However, these variants are unknown among the Colombian population. This study aimed to evaluate the single nucleotide polymorphism rs10930046 (His460Arg) in the IFIH1 gene and its ssociation with the development of psoriasis in a Colombian population. METHODS: An observational, unmatched, case-control study was performed, including 51 patients with psoriasis and 151 population controls, all with self-reported Paisa ancestry (from the Antioquia region). All individuals were genotyped for the single nucleotide polymorphism rs10930046 (His460Arg) in the IFIH1 gene, and its association with psoriasis was pursued. Both groups were demographically characterized, and cases were also assessed for clinical variables. RESULTS: Through the allelic association analysis, cases were found to have a lower frequency of the single nucleotide polymorphism rs10930046 (His460Arg) in the IFIH1 gene than controls; 5% versus 22.67%, respectively. There were no significant differences in age or sex. We also found that psoriasis vulgaris was the most common variant (78%), that about half of the cases had nail psoriasis (56%), 19.6% had psoriatic arthritis, and that 45% had some comorbidity. CONCLUSIONS: The results obtained from this study confirm that carriers of the single nucleotide polymorphism rs10930046 (His460Arg) in the IFIH1 gene have a decreased risk of developing psoriasis.
INTRODUCCIÓN: La psoriasis es una dermatosis inflamatoria crónica, con presentación clínica variable y cuya etiología involucra un componente genético importante. Alrededor del mundo se han descrito múltiples variaciones genéticas asociadas a la enfermedad. Sin embargo, en población colombiana se desconocen estas variantes. En este estudio se evalúa el polimorfismo de nucleótido único rs10930046 (His460Arg) en el gen IFIH1 y su asociación con el desarrollo de psoriasis en población colombiana. Además, se caracteriza a los individuos demográfica y clínicamente. MÉTODOS: Se realizó un estudio observacional de casos y controles, no pareado, que incluyó 51 individuos con psoriasis y 151 controles poblacionales, todos de ancestría paisa (proveniente de la región de Antioquia) auto reportada. A todos los individuos se les realizó genotipificación del polimorfismo de nucleótido único rs10930046 (His460Arg) en el gen IFIH1 y se les determinó la asociación con la enfermedad. Se caracterizaron demográficamente ambos grupos y los casos clínicamente. RESULTADOS: Se encontró que los casos presentaron una menor frecuencia del polimorfismo de nucleótido único rs10930046 (His460Arg) en el gen IFIH1 en relación a los controles, 5 versus 22,67% respectivamente, con un análisis de asociación alélico. No hubo diferencias significativas en edad ni en sexo. La psoriasis vulgar fue la variante de presentación más común (78%). Alrededor de la mitad de los casos presentaron psoriasis ungular (56%), en menor frecuencia artritis psoriásica (19,6%) y el 45% de los casos tuvo alguna comorbilidad. CONCLUSIONES: Los resultados obtenidos confirman que los portadores del polimorfismo de nucleótido único rs10930046 (His460Arg) en el gen IFIH1, presentan un riesgo disminuido de desarrollar psoriasis.
Assuntos
Helicase IFIH1 Induzida por Interferon/genética , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , HumanosRESUMO
BACKGROUND: Sleep deprivation commonly increases seizure frequency in patients with genetic generalized epilepsy, though it is unknown whether there is an increased prevalence of sleepwalking or sleep paralysis in genetic generalized epilepsy patients. Establishing this could provide insights into the bio-mechanisms or genetic architecture of both disorders. The aim of this study was to determine the prevalence of sleepwalking and sleep paralysis in a cohort of patients with genetic generalized epilepsy and their relatives in extended families. METHODS: A structured interview based on International League Against Epilepsy (ILAE) and International Classification of Sleep Disorders (ICSD-3) criteria was applied to 67 index cases and their relatives to determine genetic generalized epilepsy subtypes and assess the occurrence of sleepwalking or sleep paralysis. Bivariate analysis was performed using chi-square and Fisher exact tests. RESULTS: The prevalence of sleepwalking and sleep paralysis was 15.3% (95% confidence interval 12.1-18.9) and 11.7% (95% confidence interval 8.7-15.3), respectively. Unusually, no sleepwalkers were found among individuals displaying epilepsy with generalized tonic-clonic seizures. Approximately a quarter of the patients had either parasomnia or genetic generalized epilepsy. Over half the genetic generalized epilepsy families had at least 1 individual with sleepwalking, and more than 40% of the families had one individual with sleep paralysis. CONCLUSION: The prevalence of sleepwalking or sleep paralysis is reported for individuals with genetic generalized epilepsy and their relatives. The co-existence of either parasomnia in the genetic generalized epilepsy patients and the co-aggregation within their families let suggest that shared heritability and pathophysiological mechanisms exist between these disorders. We hypothesize that sleepwalking/sleep paralysis and genetic generalized epilepsy could be variable expression of genes in shared pathways.