Liu Ying, Wu Xueying, Fan Zhaoyang, Cheng Jingdan, Zhong Lele, Lin Yongzhong, Qu Xiaofeng
Department of Neurology, The Second Hospital of Dalian Medical University, China.
Department of Emergency, The Second Hospital of Dalian Medical University, China.
Clin Neurol Neurosurg. 2018 May;168:163-166. doi: 10.1016/j.clineuro.2018.01.034. Epub 2018 Feb 2.
We report a rare case of atherosclerotic-moyamoya syndrome (A-MMS) in an adult female with genetic variant of both ring finger 213 (RNF213) p.R4810K and p.T1727M.
A 46-year-old previously healthy, right-handed woman displayed transient slurred speech, which started to worsen four years ago. Initial magnetic resonance angiography (MRA) revealed stenosis in left middle cerebral artery (MCA), bilateral anterior cerebral artery (ACA), and left posterior cerebral artery (PCA). The patient subsequently underwent catheter angiography, which confirmed the formation of moyamoya vessels, with Suzuki's angiographic staging of grade-3 on the left side. Although the patient had been on both anti-platelet and statin therapy at the time, a follow-up examination showed further exacerbation of left MCA stenosis, along with enhanced moyamoya vessel formation. On black-blood imaging using DANTE-SPACE, there were eccentric, evolving lesions in the left MCA. We next screened for potential genetic variants, using genomic DNA samples isolated from both the patient and her immediate family members. The results showed that the patient, along with her mother, sister, and brother, possessed the heterozygous variant of the RNF213 gene, including c.14429G > A (p.R4810K) and c.5180C > T (p.T1727M). The patient's daughter did not have the variant.
Collectively, we present a unique case of A-MMS with genetic variant of RNF213 p.R4810K and p.T1727M, manifesting as progression. Based on the family tree, these two mutations are on the same RNF213 haplotype. Whether atherosclerosis is the cause of A-MMS or it further exacerbates the injury of MMD to the A-MMS patients with RNF213 gene variant is a question to be investigated.
我们报告一例成年女性的罕见动脉粥样硬化性烟雾病综合征（A-MMS）病例，该患者同时存在无名指213（RNF213）基因的p.R4810K和p.T1727M基因变异。
一名46岁、既往健康的右利手女性出现短暂性言语不清，症状于4年前开始加重。初次磁共振血管造影（MRA）显示左侧大脑中动脉（MCA）、双侧大脑前动脉（ACA）及左侧大脑后动脉（PCA）狭窄。患者随后接受了导管血管造影，证实了烟雾状血管的形成，左侧为铃木血管造影分级3级。尽管患者当时已接受抗血小板和他汀类药物治疗，但随访检查显示左侧MCA狭窄进一步加重，同时烟雾状血管形成增多。在使用DANTE-SPACE的黑血成像上，左侧MCA存在偏心、进展性病变。接下来，我们使用从患者及其直系亲属分离的基因组DNA样本筛查潜在的基因变异。结果显示，患者及其母亲、姐姐和哥哥均携带RNF213基因的杂合变异，包括c.14429G > A（p.R4810K）和c.5180C > T（p.T1727M）。患者的女儿没有该变异。
我们共同呈现了一例独特的伴有RNF213 p.R4810K和p.T1727M基因变异的A-MMS病例，表现为病情进展。根据家系图，这两个突变位于同一RNF213单倍型上。动脉粥样硬化是A-MMS的病因还是它会进一步加重RNF213基因变异的烟雾病患者的A-MMS损伤，这是一个有待研究的问题。
