Nonsyndromic Peripheral Pulmonary Artery Stenosis Is Associated With Homozygosity of RNF213 p.Arg4810Lys Regardless of Co-occurrence of Moyamoya Disease
Nonsyndromic Peripheral Pulmonary Artery Stenosis Is Associated With Homozygosity of RNF213 p.Arg4810Lys Regardless of Co-occurrence of Moyamoya Disease
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DOI：
10.1016/j.chest.2017.09.023
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发表时间：
2018-02-01
期刊：
影响因子：
9.6
通讯作者：
Kim, Duk-Kyung
中科院分区：
文献类型：
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作者：
Chang, Sung-A;Song, Ju Sun;Kim, Duk-Kyung
背景：儿童外周肺动脉狭窄(PPAs)常合并其他综合征，但青少年和成人PPAs少见，其病因尚不清楚。我们报告了与RNF213基因p.Arg4810Lys变异相关的成人起病的非综合征性PPA的临床特征。方法：我们最近遇到了一例严重的肺动脉高压合并多发性PPA和颅内外动脉病变的指征病例。由于有烟雾病(MMD)的家族史，进行了基因分析，发现该患者为RNF213p.Arg4810Lys纯合子。我们通过查阅肺动脉高压登记表和MMD登记表搜索PPA，又发现了4例PPA。结果：确诊时平均年龄26岁，男女比例为4：1。4例患者的基因分析均为RNF213p Arg4810Lys纯合子。肺血管造影显示周围肺动脉呈串珠状和/或弥漫性狭窄。值得注意的是，三名患者患有MMD，而两名患者没有。结论：RNF213p Arg4810Lys纯合子与RNF213p Arg4810Lys纯合子相关。无论是否存在MMD，RNF213变异相关的血管病变都应该被归类为成年期发病的PPA的一个独立的疾病实体。
BACKGROUND: Peripheral pulmonary arterial stenosis (PPAS) in childhood is frequently associated with other syndromes; however, PPAS in adolescents and adults is rare and its etiology is not well understood. We report the clinical characteristics of adult-onset non-syndromic PPAS associated with the p.Arg4810Lys variant of the RNF213 gene.METHODS: We recently encountered an index case of severe pulmonary hypertension with multiple PPAS and intra-and extracranial arteriopathy. Because of a family history of Moyamoya disease (MMD), genetic analysis was performed, and revealed that this patient was homozygous for RNF213 p.Arg4810Lys. We searched for PPAS by reviewing the pulmonary hypertension registry and the MMD registry, and found four more cases of PPAS. Clinical features of the five patients and their families were analyzed.RESULTS: Mean age at diagnosis of pulmonary hypertension was 26 years, and the male to female ratio was 4:1. Genetic analysis of four patients revealed that all these patients were homozygous for the RNF213 p.Arg4810Lys variant. Pulmonary angiograms showed a string of beads pattern and/or diffuse stenosis of peripheral pulmonary arteries. Notably, three patients had MMD, whereas two patients did not. The three MMD patients had multiple stenoses of extracranial arteries other than the pulmonary artery.CONCLUSIONS: PPAS in segmental or subsegmental arteries in adulthood with multiple extracranial vasculopathies was found to be associated with homozygosity for RNF213 p.Arg4810Lys. RNF213 variant-associated vasculopathy should be categorized as a discrete disease entity of adulthood-onset PPAS regardless of the presence of MMD.