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Abstract：
Activating mutations in KIT, particularly D816V, have been associated with mastocytosis. Additionally, expression of heterozygous KIT M541L has been primarily reported in patients with pediatric mastocytosis. We thus examined the prevalence of this variant in pediatric and adult patients with mastocytosis (n = 100) compared to ancestry-matched 1000 genomes controls (n = 500) and patients with idiopathic anaphylaxis (n = 23). We then compared clinical symptoms and laboratory data on patients with systemic and cutaneous mastocytosis and bone marrow histopathology on a matched cohort with and without the KIT M541L variant. Overall, the KIT M541L variant was identified in 19 individuals; the majority were diagnosed with systemic mastocytosis (89.4%) with an associated KIT D816V mutation. There were no significant differences in peripheral blood parameters between groups. Patients with mastocytosis carrying the KIT M541L variant did not demonstrate significant differences in symptomatology compared to a matched reference cohort (n = 13/81) without KIT M541L. In patients with idiopathic anaphylaxis, no significant associations were observed. This study uniquely examines the prevalence and impact of the KIT M541L variant in both adult and pediatric patients with mastocytosis further stratified by disease variant. To our knowledge, this is the first case/control study to show a significant genetic association with mastocytosis at the KIT M541L locus.
摘要：
激活KIT中的突变，特别是D816V,与肥大细胞增多症有关.此外,杂合子KITM541L的表达主要在小儿肥大细胞增多症患者中报道。因此，我们检查了这种变异在小儿和成人肥大细胞增多症患者（n=100）中的患病率，与祖先匹配的1000个基因组对照（n=500）和特发性过敏反应患者（n=23）相比。然后，我们在有和没有KITM541L变体的匹配队列中比较了全身和皮肤肥大细胞增多症患者的临床症状和实验室数据以及骨髓组织病理学。总的来说,在19例患者中发现了KITM541L变异;大多数患者被诊断为系统性肥大细胞增多症(89.4%),并伴有KITD816V突变.组间外周血参数无显著差异。与没有KITM541L的匹配参考队列（n=13/81）相比，携带KITM541L变体的肥大细胞增多症患者在症状学上没有显着差异。在特发性过敏反应患者中，未观察到显著关联.这项研究独特地检查了KITM541L变体在成年和小儿肥大细胞增多症患者中的患病率和影响，并通过疾病变体进一步分层。据我们所知,这是第一个病例/对照研究,显示与KITM541L位点的肥大细胞增多症存在显著遗传关联.
