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

Elli Katharine Greisenegger; Sara Llufriu; Angel Chamorro; Alvaro Cervera; Adriano Jimenez-Escrig; Klemens Rappersberger; Wolfgang Marik; Stefan Greisenegger; Elisabeth Stögmann; Tamara Kopp; Tim M Strom; Jörg Henes; Anne Joutel; Alexander Zimprich

doi:10.1007/s00415-020-10081-5

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

Elli Katharine Greisenegger, Sara Llufriu, Angel Chamorro, Alvaro Cervera, Adriano Jimenez-Escrig, Klemens Rappersberger, Wolfgang Marik, Stefan Greisenegger, Elisabeth Stögmann, Tamara Kopp, Tim M Strom, Jörg Henes, Anne Joutel, Alexander Zimprich

Klinische Abteilung für Haut- und Geschlechtskrankheiten (Universitätsklinikum St. Pölten)

Publikation: Beitrag in Fachzeitschrift (peer-reviewed) › Artikel in Fachzeitschrift

17 Zitate (Scopus)

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.

Originalsprache	Englisch
Seiten (von - bis)	810-816
Seitenumfang	7
Fachzeitschrift	Journal of Neurology
Jahrgang	268
Ausgabenummer	3
DOIs	https://doi.org/10.1007/s00415-020-10081-5
Publikationsstatus	Veröffentlicht - März 2021

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10.1007/s00415-020-10081-5

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Greisenegger, E. K., Llufriu, S., Chamorro, A., Cervera, A., Jimenez-Escrig, A., Rappersberger, K., Marik, W., Greisenegger, S., Stögmann, E., Kopp, T., Strom, T. M., Henes, J., Joutel, A., & Zimprich, A. (2021). A NOTCH3 homozygous nonsense mutation in familial Sneddon syndrome with pediatric stroke. Journal of Neurology, 268(3), 810-816. https://doi.org/10.1007/s00415-020-10081-5

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title = "A NOTCH3 homozygous nonsense mutation in familial Sneddon syndrome with pediatric stroke",

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.",

keywords = "Adult, Child, Codon, Nonsense, Consanguinity, Epidermal Growth Factor, Homozygote, Humans, Mutation, Receptor, Notch3/genetics, Sneddon Syndrome, Stroke/diagnostic imaging",

author = "Greisenegger, {Elli Katharine} and Sara Llufriu and Angel Chamorro and Alvaro Cervera and Adriano Jimenez-Escrig and Klemens Rappersberger and Wolfgang Marik and Stefan Greisenegger and Elisabeth St{\"o}gmann and Tamara Kopp and Strom, {Tim M} and J{\"o}rg Henes and Anne Joutel and Alexander Zimprich",

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year = "2021",

month = mar,

doi = "10.1007/s00415-020-10081-5",

language = "English",

volume = "268",

pages = "810--816",

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Greisenegger, EK, Llufriu, S, Chamorro, A, Cervera, A, Jimenez-Escrig, A, Rappersberger, K, Marik, W, Greisenegger, S, Stögmann, E, Kopp, T, Strom, TM, Henes, J, Joutel, A & Zimprich, A 2021, 'A NOTCH3 homozygous nonsense mutation in familial Sneddon syndrome with pediatric stroke', Journal of Neurology, Jg. 268, Nr. 3, S. 810-816. https://doi.org/10.1007/s00415-020-10081-5

TY - JOUR

T1 - A NOTCH3 homozygous nonsense mutation in familial Sneddon syndrome with pediatric stroke

AU - Greisenegger, Elli Katharine

AU - Llufriu, Sara

AU - Chamorro, Angel

AU - Cervera, Alvaro

AU - Jimenez-Escrig, Adriano

AU - Rappersberger, Klemens

AU - Marik, Wolfgang

AU - Greisenegger, Stefan

AU - Stögmann, Elisabeth

AU - Kopp, Tamara

AU - Strom, Tim M

AU - Henes, Jörg

AU - Joutel, Anne

AU - Zimprich, Alexander

PY - 2021/3

Y1 - 2021/3

N2 - 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.

AB - 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.

KW - Adult

KW - Child

KW - Codon, Nonsense

KW - Consanguinity

KW - Epidermal Growth Factor

KW - Homozygote

KW - Humans

KW - Mutation

KW - Receptor, Notch3/genetics

KW - Sneddon Syndrome

KW - Stroke/diagnostic imaging

UR - http://www.scopus.com/inward/record.url?scp=85091462759&partnerID=8YFLogxK

U2 - 10.1007/s00415-020-10081-5

DO - 10.1007/s00415-020-10081-5

M3 - Journal article

C2 - 32980981

SN - 0340-5354

VL - 268

SP - 810

EP - 816

JO - Journal of Neurology

JF - Journal of Neurology

IS - 3

ER -

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

Abstract

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