Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros

Banco de datos
Asunto principal
Tipo del documento
Revista
País de afiliación
Intervalo de año de publicación
1.
Brain ; 146(6): 2285-2297, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36477332

RESUMEN

The blood-brain barrier ensures CNS homeostasis and protection from injury. Claudin-5 (CLDN5), an important component of tight junctions, is critical for the integrity of the blood-brain barrier. We have identified de novo heterozygous missense variants in CLDN5 in 15 unrelated patients who presented with a shared constellation of features including developmental delay, seizures (primarily infantile onset focal epilepsy), microcephaly and a recognizable pattern of pontine atrophy and brain calcifications. All variants clustered in one subregion/domain of the CLDN5 gene and the recurrent variants demonstrate genotype-phenotype correlations. We modelled both patient variants and loss of function alleles in the zebrafish to show that the variants analogous to those in patients probably result in a novel aberrant function in CLDN5. In total, human patient and zebrafish data provide parallel evidence that pathogenic sequence variants in CLDN5 cause a novel neurodevelopmental disorder involving disruption of the blood-brain barrier and impaired neuronal function.


Asunto(s)
Microcefalia , Animales , Humanos , Microcefalia/genética , Claudina-5/genética , Claudina-5/metabolismo , Pez Cebra/metabolismo , Barrera Hematoencefálica/metabolismo , Convulsiones/genética , Síndrome
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA