结节性硬化症合并双肾巨大血管平滑肌脂肪瘤一家系TSC基因突变分析  

TSC gene in a family with tuberous sclerosis complicated with giant bilateral renal angiomyolipoma

作　　者：张瑞晓 王建红[2] 王青[3] 韩玥 郎艳华 刘学军[5] 邵乐平[1] Zhang Ruixiao;Wang Jianhong;Wang Qing;Han Yue;Lang Yanhua;Liu Xuejun;Shao Leping(Department of Nephrology,Qingdao Municipal Hospital Affiliated to Qingdao University,Qingdao 266071,China;Department of Ultrasound,Affiliated Hospital of Qingdao University,Qingdao 266003, China;Department of Ophthalmology,Affiliated Hospital of Qingdao University,Qingdao 266003,China;Department of Nursing,Affiliated Hospital of Qingdao University,Qingdao 266003,China;Department of Radiology,Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属青岛市市立医院肾内科,266071 [2]青岛大学附属医院超声科,青岛266003 [3]青岛大学附属医院眼科,青岛266003 [4]青岛大学附属医院护理部,青岛266003 [5]青岛大学附属医院放射科,青岛266003

出　　处：《中华神经医学杂志》2019年第1期76-79,共4页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金面上项目(81170653,81873594).

摘　　要：目的 描述结节性硬化症(TSC)伴发双肾巨大血管平滑肌脂肪瘤一家系患者的临床特征并对该家系进行致病基因突变分析。 方法 整理患者临床资料并通过二代测序对该家系TSC1和TSC2基因进行测序分析。通过迷你基因(pSPL3外显子捕获质粒)构建与表达对可疑剪切突变进行验证,最后以患者RNA对其进行体内验证。 结果 患者临床表现典型,以双肾巨大血管平滑肌脂肪瘤为主,同时伴有面部血管纤维瘤、甲周纤维瘤、肺淋巴管肌瘤病、室管膜下钙化结节和视网膜错构瘤等表现。基因分析发现1个新的TSC2基因杂合突变(c.3610G>A)。在蛋白水平上预测该突变为错义突变(p.Gly1204Arg),但在转录水平上,迷你基因及RNA分析均验证该突变为剪切突变。 结论 本研究新发现1个突变位点与TSC有关,该突变同时导致氨基酸替代和异常剪切。Objective To describe the clinical characteristics of a family with tuberous sclerosis (TSC) complicated with giant bilateral renal angiomyolipoma, and to analyze the causal genetic mutations. Methods All coding regions of TSC1 gene and TSC2 gene were analyzed by next generation sequencing. The potential effect on abnormal splicing was confirmed by minigene assay based on the pSPL3 exon capture vector and was validated in vivo with the patient's RNA. Results The clinical manifestations of the proband were typical. Bilateral large renal angiomyolipomas were her principal clinical features. Besides, facial angiofibroma, periungual fibroma, lung lymphangioleiomyomatosis and subependymal nodule were also noted. A novel heterozygous variant of TSC2 gene (c.3610G>A) was identified. On the protein level, this variant was presumed to be missense mutation (p. Gly1204Arg);however, the splicing assay revealed that this mutation also led to aberrant splicing with the whole exon 29 skipping on the transcripts level. Conclusion A novel mutation c. 3610G>A, contributing to aberrant splicing and missense alteration (p. Gly1204Arg), is identified in association with TSC.

关 键 词：结节性硬化症 肾血管平滑肌脂肪瘤 TSC基因 

分 类 号：R596.1[医药卫生—内科学] R737.11[医药卫生—临床医学]