Genetics and phenotypic heterogeneity of Dent disease: the dark side of the moon.
Genetics and phenotypic heterogeneity of Dent disease: the dark side of the moon.
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DOI：
10.1007/s00439-020-02219-2
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发表时间：
2021-03
期刊：
影响因子：
5.3
通讯作者：
Calò LA
中科院分区：
文献类型：
--
作者：
Gianesello L;Del Prete D;Anglani F;Calò LA
牙本质病是一种罕见的遗传性近端小管病变，这是认识不足。其表型异质性导致了同一疾病的几种不同分类，但现在广泛接受的是，低分子量蛋白尿，高钙尿和肾钙质沉着症/肾结石的三联征是Dent病的特征性。虽然已知CLCN 5和OCRL基因突变会导致Dent病，但在约25-35%的病例中没有发现此类突变，这使得诊断更具挑战性。本文从另一个角度概述了目前对Dent病的认识。从登特病的历史开始，并回顾了有和没有遗传特征的患者的临床细节，我们讨论了这种疾病的表型和遗传异质性。我们特别关注所有那些可能导致误诊的混淆临床体征和症状。我们还试图揭示一个隐藏的方面，登特病。虽然它是一种近端小管病变，但其误诊可能导致患者接受肾活检。事实上，一些患有登特病的个体具有高级别的蛋白尿，伴有或不伴有血尿，如在肾小球病或不明原因的慢性肾病的临床背景中。虽然肾小球损害经常记录在登氏病患者的活检，目前没有可靠的证据表明肾活检是诊断或预后价值。我们回顾了这些患者肾小管和肾小球损伤的组织病理学报告，并讨论了CLCN 5和OCRL基因在肾小球功能中的作用。本文的在线版本（10.1007/s 00439 -020-02219-2）包含补充材料，可供授权用户使用。
Dent disease is a rare genetic proximal tubulopathy which is under-recognized. Its phenotypic heterogeneity has led to several different classifications of the same disorder, but it is now widely accepted that the triad of symptoms low-molecular-weight proteinuria, hypercalciuria and nephrocalcinosis/nephrolithiasis are pathognomonic of Dent disease. Although mutations on the CLCN5 and OCRL genes are known to cause Dent disease, no such mutations are found in about 25–35% of cases, making diagnosis more challenging. This review outlines current knowledge regarding Dent disease from another perspective. Starting from the history of Dent disease, and reviewing the clinical details of patients with and without a genetic characterization, we discuss the phenotypic and genetic heterogeneity that typifies this disease. We focus particularly on all those confounding clinical signs and symptoms that can lead to a misdiagnosis. We also try to shed light on a concealed aspect of Dent disease. Although it is a proximal tubulopathy, its misdiagnosis may lead to patients undergoing kidney biopsy. In fact, some individuals with Dent disease have high-grade proteinuria, with or without hematuria, as in the clinical setting of glomerulopathy, or chronic kidney disease of uncertain origin. Although glomerular damage is frequently documented in Dent disease patients’ biopsies, there is currently no reliable evidence of renal biopsy being of either diagnostic or prognostic value. We review published histopathology reports of tubular and glomerular damage in these patients, and discuss current knowledge regarding the role of CLCN5 and OCRL genes in glomerular function. The online version of this article (10.1007/s00439-020-02219-2) contains supplementary material, which is available to authorized users.
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影响因子：
13.6
作者：
Bothwell, Susan P.;Chan, Emily;Nussbaum, Robert L.
通讯作者：
Nussbaum, Robert L.
影响因子：
5.1
作者：
Bokenkamp, Arend;Bockenhauer, Detlef;Ludwig, Michael
通讯作者：
Ludwig, Michael
影响因子：
3
作者：
Beara-Lasic, Lada;Cogal, Andrea;Lieske, John C.
通讯作者：
Lieske, John C.
DOI：
10.1016/j.bbrc.2003.09.057
发表时间：
2003-10-17
影响因子：
3.1
作者：
Carr, G;Simmons, N;Sayer, J
通讯作者：
Sayer, J
影响因子：
5.2
作者：
Addis, Maria;Meloni, Cristiana;Anglani, Franca
通讯作者：
Anglani, Franca