A NOTCH3 homozygous nonsense mutation in familial Sneddon syndrome with pediatric stroke

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 homoz...

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Detalles Bibliográficos
Autores principales: Greisenegger, Elli Katharine, Llufriu, Sara, Chamorro, Angel, Cervera, Alvaro, Jimenez-Escrig, Adriano, Rappersberger, Klemens, Marik, Wolfgang, Greisenegger, Stefan, Stögmann, Elisabeth, Kopp, Tamara, Strom, Tim M., Henes, Jörg, Joutel, Anne, Zimprich, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Original Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914241/
https://www.ncbi.nlm.nih.gov/pubmed/32980981
http://dx.doi.org/10.1007/s00415-020-10081-5
Descripción
Sumario: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.

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