A NOTCH3 homozygous nonsense mutation in familial Sneddon syndrome with pediatric stroke
| Autor: | Alexander Zimprich, Anne Joutel, Klemens Rappersberger, Stefan Greisenegger, Elisabeth Stögmann, Ángel Chamorro, Tim M. Strom, Álvaro Cervera, Elli K. Greisenegger, Wolfgang Marik, Tamara Kopp, Jörg Henes, Sara Llufriu, Adriano Jimenez-Escrig |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Oncology medicine.medical_specialty Neurology Nonsense mutation CADASIL 030204 cardiovascular system & hematology Sneddon syndrome Consanguinity 03 medical and health sciences 0302 clinical medicine NOTCH3 Internal medicine Humans Medicine Pediatric stroke Child Receptor Notch3 Stroke Livedo reticularis Original Communication Epidermal Growth Factor business.industry Homozygote medicine.disease ddc Sneddon Syndrome Homozygous nonsense mutation Codon Nonsense Mutation Mutation (genetic algorithm) Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neurology |
| ISSN: | 1432-1459 0340-5354 |
| DOI: | 10.1007/s00415-020-10081-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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