Phi Ji Hoon, Choi Jung Won, Seong Moon-Woo, Kim Tackeun, Moon Youn Joo, Lee Joongyub, Koh Eun Jung, Ryu Seul Ki, Kang Tae Hee, Bang Jae Seung, Oh Chang Wan, Park Sung Sup, Lee Ji Yeoun, Wang Kyu-Chang, Kim Seung-Ki
Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul National University College of Medicine;
Department of Neurosurgery, Samsung Medical Center;
J Neurosurg Pediatr. 2016 Jun;17(6):717-22. doi: 10.3171/2015.10.PEDS15537. Epub 2016 Feb 5.
OBJECTIVE In a minority of patients with neurofibromatosis Type 1 (NF-1), cerebral vasculopathy reminiscent of moyamoya disease develops. This phenomenon is called moyamoya syndrome (MMS), but there are no known risk factors for the prediction of MMS in NF-1 patients. Polymorphism of the RNF213 gene has exhibited strong associations with familial and sporadic moyamoya disease and other cerebral vasculopathies. The aim of this study is to find whether the RNF213 c.14576G>A variant is associated with MMS development in the NF-1 population or not. METHODS The MMS group included 16 NF-1 patients with documented MMS. The control group consisted of 97 NF-1 patients without MMS. Genomic DNA samples were obtained from the saliva or blood of both groups, and the presence of the RNF213 c.14576G>A variant was assessed by Sanger sequencing. RESULTS In the MMS group, 3 patients had the RNF213 c.14576G>A variant (18.7%), whereas no patients with this genetic variation were observed in the control group (0%). There was a meaningful association between the RNF213 c.14576G>A variant and MMS development (p = 0.0024). The crude odds ratio was calculated as 50.57 (95% CI 1.57-1624.41). All 3 patients with MMS and the c.14576G>A variant were diagnosed with MMS at an early age and had bilateral involvement. CONCLUSIONS The RNF213 c.14576G>A variant is more common in NF-1 patients who develop MMS than in NF-1 patients without MMS. This variant might be a susceptibility gene for the NF-1-moyamoya connection.
在少数1型神经纤维瘤病（NF-1）患者中，会出现类似烟雾病的脑血管病变。这种现象被称为烟雾病综合征（MMS），但目前尚无已知的危险因素可用于预测NF-1患者的MMS。RNF213基因的多态性已显示出与家族性和散发性烟雾病以及其他脑血管病变密切相关。本研究的目的是探究RNF213基因c.14576G>A变异是否与NF-1人群中MMS的发生有关。方法：MMS组包括16例有记录的NF-1合并MMS患者。对照组由97例无MMS的NF-1患者组成。从两组患者的唾液或血液中获取基因组DNA样本，并通过桑格测序评估RNF213基因c.14576G>A变异的存在情况。结果：在MMS组中，3例患者存在RNF213基因c.14576G>A变异（18.7%），而在对照组中未观察到有此基因变异的患者（0%）。RNF213基因c.14576G>A变异与MMS的发生之间存在显著关联（p = 0.0024）。粗略比值比计算为50.57（95%可信区间1.57 - 1624.41）。所有3例患有MMS且存在c.14576G>A变异的患者均在早年被诊断为MMS，且双侧受累。结论：RNF213基因c.14576G>A变异在发生MMS的NF-1患者中比在无MMS的NF-1患者中更常见。该变异可能是NF-1与烟雾病关联的易感基因。
