Department of Dermatology and Venereology, University Hospital of St. Pölten, Karl Landsteiner University of Health Sciences, St. Pölten, Austria.
Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
J Neurol. 2021 Mar;268(3):810-816. doi: 10.1007/s00415-020-10081-5. Epub 2020 Sep 26.
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.
斯内登综合征是一种罕见的疾病，影响小血管和中等大小的血管，其特征是网状青斑和中风的联合发生。我们对一个有血缘关系的家族中 2 名患有儿童期起病中风的受影响的兄弟姐妹进行了全外显子组测序（WES），并在 NOTCH3 的表皮生长因子重复（EGFr）19 中发现了一个纯合无义突变，p.(Arg735Ter)。对另外 6 名成年起病中风的病例进行 WES 检测发现，2 名患者携带潜在的 NOTCH3 下游基因 ANGPTL4 和 PALLD 的杂合失活变异。我们的研究结果表明，NOTCH3 信号传导受损是一种潜在的疾病机制，而 NOTCH3 的双等位基因失活突变是导致伴有儿童期中风的家族性斯内登综合征的原因。
