A NOTCH3 homozygous nonsense mutation in familial Sneddon syndrome with pediatric stroke.
J Neurol
; 268(3): 810-816, 2021 Mar.
Article
en En
| MEDLINE
| ID: mdl-32980981
ABSTRACT
Sneddon syndrome is a rare disorder affecting small and medium-sized blood vessels that is characterized by the association of livedo reticularis and stroke. We performed whole-exome sequencing (WES) in 2 affected siblings of a consanguineous family with childhood-onset stroke and identified a homozygous nonsense mutation within the epidermal growth factor repeat (EGFr) 19 of NOTCH3, p.(Arg735Ter). WES of 6 additional cases with adult-onset stroke revealed 2 patients carrying heterozygous loss-of-function variants in putative NOTCH3 downstream genes, ANGPTL4, and PALLD. Our findings suggest that impaired NOTCH3 signaling is one underlying disease mechanism and that bi-allelic loss-of-function mutation in NOTCH3 is a cause of familial Sneddon syndrome with pediatric stroke.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Síndrome de Sneddon
/
Accidente Cerebrovascular
/
Receptor Notch3
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Child
/
Humans
Idioma:
En
Revista:
J Neurol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Austria