Clinical spectrum and pathogenesis of nephronophthisis

被引：30

作者：

Benzing, Thomas ^{[1
,2
]}

Schermer, Bernhard ^{[1
,2
]}

机构：

[1] Univ Cologne, Dept Internal Med 2, D-50937 Cologne, Germany

[2] Univ Cologne, Ctr Mol Med Cologne, D-50937 Cologne, Germany

来源：

CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION | 2012年 / 21卷 / 03期

关键词：

Hippo; intraflagellar transport; nephronophthisis; primary cilia; Wnt; JOUBERT-SYNDROME; JUVENILE NEPHRONOPHTHISIS; HIPPO PATHWAY; MECKEL SYNDROME; DOMAIN PROTEIN; BETA-CATENIN; CILIARY; GENE; MUTATIONS; CILIOPATHY;

D O I：

10.1097/MNH.0b013e3283520f17

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Purpose of review Nephronophthisis (NPH) comprises a group of autosomal recessive cystic kidney diseases and is the most frequent genetic cause of end-stage renal disease in children and adolescents. Causative mutations in more than a dozen genes have been identified that encode for the NPH protein family. Almost all of these proteins localize to primary cilia leading to the classification of NPH as a ciliopathy. The purpose of this review is to highlight the latest research on the molecular pathogenesis of the ciliopathy NPH. Recent findings Recent identification of novel disease causing genes and research on the localization and signaling function of nephrocystins have paved the way to a more detailed understanding of the molecular and cellular pathology of NPH and associated ciliopathies. Summary Here we discuss the most recently identified NPH related genes, the role of the NPH protein complex in ciliary biology and recently discovered functions of NPH proteins in cellular signaling.

引用

页码：272 / 278

页数：7

共 52 条

[1] Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis [J].

Attanasio, Massimo ;

Uhlenhaut, N. Henriette ;

Sousa, Vitor H. ;

O'Toole, John F. ;

Otto, Edgar ;

Anlag, Katrin ;

Klugmann, Claudia ;

Treier, Anna-Corina ;

Helou, Juliana ;

Sayer, John A. ;

Seelow, Dominik ;

Nurnberg, Gudrun ;

Becker, Christian ;

Chudley, Albert E. ;

Nurnberg, Peter ;

Hildebrandt, Friedhelm ;

Treier, Mathias .

NATURE GENETICS, 2007, 39 (08) :1018-1024

[2] Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus [J].

Badano, JL ;

Kim, JC ;

Hoskins, BE ;

Lewis, RA ;

Ansley, SJ ;

Cutler, DJ ;

Castellan, C ;

Beales, PL ;

Leroux, MR ;

Katsanis, N .

HUMAN MOLECULAR GENETICS, 2003, 12 (14) :1651-1659

[3] A homozygous mutation in INVS causing juvenile nephronophthisis with abnormal reactivity of the Wnt/beta-catenin pathway [J].

Bellavia, Salvatore ;

Dahan, Karin ;

Terryn, Sara ;

Cosyns, Jean-Pierre ;

Devuyst, Olivier ;

Pirson, Yves .

NEPHROLOGY DIALYSIS TRANSPLANTATION, 2010, 25 (12) :4097-4102

[4] Loss of nephrocystin-3 function can cause embryonic lethality, meckel-gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia [J].

Bergmann, Carsten ;

Fliegauf, Manfred ;

Bruechle, Nadina Ortiz ;

Frank, Valeska ;

Olbrich, Heike ;

Kirschner, Jan ;

Schermer, Bernhard ;

Schmedding, Ingolf ;

Kispert, Andreas ;

Kraenzlin, Bettina ;

Nuernberg, Gudrun ;

Becker, Christian ;

Grimm, Tiemo ;

Girschick, Gundula ;

Lynch, Sally A. ;

Kelehan, Peter ;

Senderek, Jan ;

Neuhaus, Thomas J. ;

Stallmach, Thomas ;

Zentgraf, Hanswalter ;

Nuernberg, Peter ;

Gretz, Norbert ;

Lo, Cecilia ;

Lienkamp, Soeren ;

Schaefer, Tobias ;

Walz, Gerd ;

Benzing, Thomas ;

Zerres, Klaus ;

Omran, Heymut .

AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 82 (04) :959-970

[5] Lights on for aminopeptidases in cystic kidney disease [J].

Boettinger, Erwin P. .

JOURNAL OF CLINICAL INVESTIGATION, 2010, 120 (03) :660-663

[6] Ciliopathies with Skeletal Anomalies and Renal Insufficiency due to Mutations in the IFT-A Gene WDR19 [J].

Bredrup, Cecilie ;

Saunier, Sophie ;

Oud, Machteld M. ;

Fiskerstrand, Torunn ;

Hoischen, Alexander ;

Brackman, Damien ;

Leh, Sabine M. ;

Midtbo, Marit ;

Filhol, Emilie ;

Bole-Feysot, Christine ;

Nitschke, Patrick ;

Gilissen, Christian ;

Haugen, Olav H. ;

Sanders, Jan-Stephan F. ;

Stolte-Dijkstra, Irene ;

Mans, Dorus A. ;

Steenbergen, Eric J. ;

Hamel, Ben C. J. ;

Matignon, Marie ;

Pfundt, Rolph ;

Jeanpierre, Cecile ;

Boman, Helge ;

Rodahl, Eyvind ;

Veltman, Joris A. ;

Knappskog, Per M. ;

Knoers, Nine V. A. M. ;

Roepman, Ronald ;

Arts, Heleen H. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2011, 89 (05) :634-643

[7] Control of the Wnt pathways by nephrocystin-4 is required for morphogenesis of the zebrafish pronephros [J].

Burckle, Celine ;

Gaude, Helori-Mael ;

Vesque, Christine ;

Silbermann, Flora ;

Salomon, Remi ;

Jeanpierre, Cecile ;

Antignac, Corinne ;

Saunier, Sophie ;

Schneider-Maunoury, Sylvie .

HUMAN MOLECULAR GENETICS, 2011, 20 (13) :2611-2627

[8] Kif3a constrains β-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms [J].

Corbit, Kevin C. ;

Shyer, Amy E. ;

Dowdle, William E. ;

Gaulden, Julie ;

Singla, Veena ;

Reiter, Jeremy F. .

NATURE CELL BIOLOGY, 2008, 10 (01) :70-U54

[9] CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content [J].

Craige, Branch ;

Tsao, Che-Chia ;

Diener, Dennis R. ;

Hou, Yuqing ;

Lechtreck, Karl-Ferdinand ;

Rosenbaum, Joel L. ;

Witman, George B. .

JOURNAL OF CELL BIOLOGY, 2010, 190 (05) :927-940

[10] TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum [J].

Davis, Erica E. ;

Zhang, Qi ;

Liu, Qin ;

Diplas, Bill H. ;

Davey, Lisa M. ;

Hartley, Jane ;

Stoetzel, Corinne ;

Szymanska, Katarzyna ;

Ramaswami, Gokul ;

Logan, Clare V. ;

Muzny, Donna M. ;

Young, Alice C. ;

Wheeler, David A. ;

Cruz, Pedro ;

Morgan, Margaret ;

Lewis, Lora R. ;

Cherukuri, Praveen ;

Maskeri, Baishali ;

Hansen, Nancy F. ;

Mullikin, James C. ;

Blakesley, Robert W. ;

Bouffard, Gerard G. ;

Gyapay, Gabor ;

Rieger, Susanne ;

Toenshoff, Burkhard ;

Kern, Ilse ;

Soliman, Neveen A. ;

Neuhaus, Thomas J. ;

Swoboda, Kathryn J. ;

Kayserili, Hulya ;

Gallagher, Tomas E. ;

Lewis, Richard A. ;

Bergmann, Carsten ;

Otto, Edgar A. ;

Saunier, Sophie ;

Scambler, Peter J. ;

Beales, Philip L. ;

Gleeson, Joseph G. ;

Maher, Eamonn R. ;

Attie-Bitach, Tania ;

Dollfus, Helene ;

Johnson, Colin A. ;

Green, Eric D. ;

Gibbs, Richard A. ;

Hildebrandt, Friedhelm ;

Pierce, Eric A. ;

Katsanis, Nicholas .

NATURE GENETICS, 2011, 43 (03) :189-U28

← 1 2 3 4 5 6 →