Renal cystic disease in tuberous sclerosis: Role of the polycystic kidney disease 1 gene
Renal cystic disease in tuberous sclerosis: Role of the polycystic kidney disease 1 gene
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DOI：
10.1086/514888
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发表时间：
1997-10-01
影响因子：
9.8
通讯作者：
Harris, PC
中科院分区：
文献类型：
--
作者：
Sampson, JR;Maheshwar, MM;Harris, PC
结节性硬化症是一种常染色体显性遗传特征，其特征是在许多器官发展成错构瘤状生长。肾囊肿也是常见的表现。结节性硬化症和常染色体显性遗传性多囊肾病的主要基因TSC2和PKD1分别位于染色体16p13.3上相邻，提示PKD1在结节性硬化性肾囊性疾病的病因学中起作用。我们研究了27例无血缘关系的结节性硬化症和肾囊性疾病。回顾临床病史和放射学特征，并评估肾功能。我们使用脉冲场和常规凝胶电泳法和FISH技术寻找TSC2和PKD1基因座的突变。22例患者存在TSC2和PKD1的连续缺失。在17例结构缺失的患者中，囊性病变严重，并有早期肾功能不全。1例TSC2缺失，仅有PKD13‘端非编码区缺失的患者囊性变少。四名患者为体细胞马赛克；他们的囊性疾病的严重程度差别很大。在3名宪法缺失的患者中，父母也表现出嵌合体和轻度囊性疾病。5例无邻近缺失的患者有相对轻微的囊性病变，其中3例有TSC2大体重排，2例未发现突变。结节性硬化症中显著的肾囊性病变通常反映了PKD1基因的突变，而TSC2和PKD1大片段缺失的嵌合体是一种常见的现象。
Tuberous sclerosis is an autosomal dominant trait characterized by the development of hamartomatous growths in many organs. Renal cysts are also a frequent manifestation. Major genes for tuberous sclerosis and autosomal dominant polycystic kidney disease, TSC2 and PKD1, respectively, lie adjacent to each other at chromosome 16p13.3, suggesting a role for PKD1 in the etiology of renal cystic disease in tuberous sclerosis. We studied 27 unrelated patients with tuberous sclerosis and renal cystic disease. Clinical histories and radiographic features were reviewed, and renal function was assessed. We sought mutations at the TSC2 and PKD1 loci, using pulsed field-and conventional-gel electrophoresis and FISH. Twenty-two patients had contiguous deletions of TSC2 and PKD1. In 17 patients with constitutional deletions, cystic disease was severe, with early renal insufficiency. One patient with deletion of TSC2 and of only the 3' UTR of PKD1 had few cysts. Four patients were somatic mosaics; the severity of their cystic disease varied considerably. Mosaicism and mild cystic disease also were demonstrated in parents of 3 of the constitutionally deleted patients. Five patients without contiguous deletions had relatively mild cystic disease, 3 of whom had gross rearrangements of TSC2 and 2 in whom no mutation was identified. Significant renal cystic disease in tuberous sclerosis usually reflects mutational involvement of the PKD1 gene, and mosaicism for large deletions of TSC2 and PKD1 is a frequent phenomenon.