Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
Dipartimento di Medicina di Precisione, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.
PLoS One. 2018 Jul 12;13(7):e0200446. doi: 10.1371/journal.pone.0200446. eCollection 2018.
Moyamoya angiopathy is a progressive cerebral vasculopathy. The p.R4810K substitution in RNF213 has previously been linked to moyamoya disease in Asian populations. When associated with other medical conditions, such as neurofibromatosis type 1, this vasculopathy is frequently reported as moyamoya syndrome. Intriguingly, most cases of moyamoya-complicated neurofibromatosis type 1 have been described in Caucasians, inverting the population ratio observed in Asians, although prevalence of neurofibromatosis type 1 is constant worldwide. Our aim was to investigate whether, among Caucasians, additive genetic factors may contribute to the occurrence of moyamoya in neurofibromatosis type 1.
Whole exome sequencing was carried out on an Italian family with moyamoya-complicated neurofibromatosis type 1 to identify putative genetic modifiers independent of the NF1 locus and potentially involved in moyamoya pathogenesis. Results were validated in an unrelated family of German ancestry.
We identified the p.P186S substitution (rs35857561) in MRVI1 that segregated with moyamoya syndrome in both the Italian and German family.
The rs35857561 polymorphism in MRVI1 may be a genetic susceptibility factor for moyamoya in European patients with neurofibromatosis type 1. MRVI1 is a functional partner of ITPR1, PRKG1 and GUCY1A3, which are involved in response to nitric oxide. Mutations in GUCY1A3 have been recently linked to a recessive syndromic form of moyamoya with esophageal achalasia.
烟雾病是一种进行性的脑血管病。RNF213 中的 p.R4810K 取代先前与亚洲人群的烟雾病有关。当与其他医学状况（如神经纤维瘤病 1 型）相关联时，这种血管病常被报告为烟雾病综合征。有趣的是，大多数伴有神经纤维瘤病 1 型的烟雾病病例发生在白种人群中，与亚洲人群观察到的比例相反，尽管神经纤维瘤病 1 型的患病率在全球范围内是恒定的。我们的目的是研究在白种人群中，附加遗传因素是否可能导致神经纤维瘤病 1 型发生烟雾病。
对一个意大利伴有神经纤维瘤病 1 型合并烟雾病的家系进行全外显子组测序，以鉴定与 NF1 基因座无关且可能参与烟雾病发病机制的潜在遗传修饰因子。结果在一个具有德国血统的无关家系中得到了验证。
我们鉴定出了 MRVI1 中的 p.P186S 取代（rs35857561），该取代在意大利和德国家系中与烟雾病综合征共分离。
MRVI1 中的 rs35857561 多态性可能是欧洲神经纤维瘤病 1 型患者发生烟雾病的遗传易感因素。MRVI1 是 ITPR1、PRKG1 和 GUCY1A3 的功能伴侣，这些基因参与对一氧化氮的反应。GUCY1A3 的突变最近与一种隐性综合征形式的烟雾病伴食管失弛缓症有关。
