| |
Mutations of the SLIT2–ROBO2 pathway genes SLIT2 and SRGAP1 confer risk for congenital anomalies of the kidney and urinary tract
- 作者:Daw-Yang Hwang ; Stefan Kohl ; Xueping Fan ; Asaf Vivante ; Stefanie Chan…
- 刊名:Human Genetics
- 出版年:2015
- 出版时间:August 2015
- 年:2015
- 卷:134
- 期:8
- 页码:905-916
- 全文大小:3,502 KB
- 参考文献:Bertoli-Avella AM, Conte ML, Punzo F, de Graaf BM, Lama G, La Manna A, Polito C, Grassia C, Nobili B, Rambaldi PF, Oostra BA, Perrotta S (2008) ROBO2 gene variants are associated with familial vesicoureteral reflux. J Am Soc Nephrol 19:825-31. doi:10.-681/?ASN.-007060692 PubMed Central PubMed View Article
Boyden LM, Choi M, Choate KA, Nelson-Williams CJ, Farhi A, Toka HR, Tikhonova IR, Bjornson R, Mane SM, Colussi G, Lebel M, Gordon RD, Semmekrot BA, Poujol A, Valimaki MJ, De Ferrari ME, Sanjad SA, Gutkin M, Karet FE, Tucci JR, Stockigt JR, Keppler-Noreuil KM, Porter CC, Anand SK, Whiteford ML, Davis ID, Dewar SB, Bettinelli A, Fadrowski JJ, Belsha CW, Hunley TE, Nelson RD, Trachtman H, Cole TR, Pinsk M, Bockenhauer D, Shenoy M, Vaidyanathan P, Foreman JW, Rasoulpour M, Thameem F, Al-Shahrouri HZ, Radhakrishnan J, Gharavi AG, Goilav B, Lifton RP (2012) Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. Nature 482:98-02. doi:10.-038/?nature10814 PubMed Central PubMed View Article Brakeman P (2008) Vesicoureteral reflux, reflux nephropathy, and end-stage renal disease. Adv Urol. doi:10.-155/-008/-08949 PubMed Central PubMed Brose K, Bland KS, Wang KH, Arnott D, Henzel W, Goodman CS, Tessier-Lavigne M, Kidd T (1999) Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 96:795-06PubMed View Article Chaki M, Airik R, Ghosh AK, Giles RH, Chen R, Slaats GG, Wang H, Hurd TW, Zhou W, Cluckey A, Gee HY, Ramaswami G, Hong CJ, Hamilton BA, Cervenka I, Ganji RS, Bryja V, Arts HH, van Reeuwijk J, Oud MM, Letteboer SJ, Roepman R, Husson H, Ibraghimov-Beskrovnaya O, Yasunaga T, Walz G, Eley L, Sayer JA, Schermer B, Liebau MC, Benzing T, Le Corre S, Drummond I, Janssen S, Allen SJ, Natarajan S, O’Toole JF, Attanasio M, Saunier S, Antignac C, Koenekoop RK, Ren H, Lopez I, Nayir A, Stoetzel C, Dollfus H, Massoudi R, Gleeson JG, Andreoli SP, Doherty DG, Lindstrad A, Golzio C, Katsanis N, Pape L, Abboud EB, Al-Rajhi AA, Lewis RA, Omran H, Lee EY, Wang S, Sekiguchi JM, Saunders R, Johnson CA, Garner E, Vanselow K, Andersen JS, Shlomai J, Nurnberg G, Nurnberg P, Levy S, Smogorzewska A, Otto EA, Hildebrandt F (2012) Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. Cell 150:533-48. doi:10.-016/?j.?cell.-012.-6.-28 PubMed Central PubMed View Article Costantini F, Shakya R (2006) GDNF/Ret signaling and the development of the kidney. BioEssays 28:117-27. doi:10.-002/?bies.-0357 PubMed View Article Dobson MG, Darlow JM, Hunziker M, Green AJ, Barton DE, Puri P (2013) Heterozygous non-synonymous ROBO2 variants are unlikely to be sufficient to cause familial vesicoureteric reflux. Kidney Int 84:327-37. doi:10.-038/?ki.-013.-00 PubMed View Article Durbec P, Marcos-Gutierrez CV, Kilkenny C, Grigoriou M, Wartiowaara K, Suvanto P, Smith D, Ponder B, Costantini F, Saarma M et al (1996) GDNF signalling through the Ret receptor tyrosine kinase. Nature 381:789-93. doi:10.-038/-81789a0 PubMed View Article Fan X, Li Q, Pisarek-Horowitz A, Rasouly HM, Wang X, Bonegio RG, Wang H, McLaughlin M, Mangos S, Kalluri R, Holzman LB, Drummond IA, Brown D, Salant DJ, Lu W (2012) Inhibitory effects of Robo2 on nephrin: a crosstalk between positive and negative signals regulating podocyte structure. Cell Rep 2:52-1. doi:10.-016/?j.?celrep.-012.-6.-02 PubMed Central PubMed View Article Gbadegesin RA, Brophy PD, Adeyemo A, Hall G, Gupta IR, Hains D, Bartkowiak B, Rabinovich CE, Chandrasekharappa S, Homstad A, Westreich K, Wu G, Liu Y, Holanda D, Clarke J, Lavin P, Selim A, Miller S, Wiener JS, Ross SS, Foreman J, Rotimi C, Winn MP (2013) TNXB mutations can cause vesicoureteral reflux. J Am Soc Nephrol 24:1313-322. doi:10.-681/?ASN.-012121148 PubMed Central PubMed View Article Grieshammer U, Le M, Plump AS, Wang F, Tessier-Lavigne M, Martin GR (2004) SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site. Dev Cell 6:709-17 (pii: S153458070400108X) PubMed View Article Halbritter J, Diaz K, Chaki M, Porath JD, Tarrier B, Fu C, Innis JL, Allen SJ, Lyons RH, Stefanidis CJ, Omran H, Soliman NA, Otto EA (2012) High-throughput mutation analysis in patients with a nephronophthisis-associated ciliopathy applying multiplexed barcoded array-based PCR amplification and next-generation sequencing. J Med Genet 49:756-67. doi:10.-136/?jmedgenet-2012-100973 PubMed View Article Halbritter J, Porath JD, Diaz KA, Braun DA, Kohl S, Chaki M, Allen SJ, Soliman NA, Hildebrandt F, Otto EA (2013) Identification of 99 novel mutations in a worldwide cohort of 1,056 patients with a nephronophthisis-related ciliopathy. Hum Genet 132:865-84. doi:10.-007/?s00439-013-1297-0 PubMed View Article Humbert C, Silbermann F, Morar B, Parisot M, Zarhrate M, Masson C, Tores F, Blanchet P, Perez MJ, Petrov Y, Khau Van Kien P, Roume J, Leroy B, G - 作者单位:Daw-Yang Hwang (1) (12)
Stefan Kohl (1) Xueping Fan (2) Asaf Vivante (1) Stefanie Chan (2) Gabriel C. Dworschak (1) (4) Julian Schulz (1) Albertien M. van Eerde (3) Alina C. Hilger (4) Heon Yung Gee (1) Tracie Pennimpede (5) Bernhard G. Herrmann (5) Glenn van de Hoek (3) Kirsten Y. Renkema (3) Christoph Schell (13) (19) (6) Tobias B. Huber (14) (6) Heiko M. Reutter (15) (4) Neveen A. Soliman (16) (7) Natasa Stajic (17) (8) Radovan Bogdanovic (17) (8) Elijah O. Kehinde (9) Richard P. Lifton (10) (18) (20) Velibor Tasic (11) Weining Lu (2) Friedhelm Hildebrandt (1) (20)
1. Division of Nephrology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA 12. Division of Nephrology, Department of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 2. Renal Section, Department of Medicine, Boston University Medical Center, 650 Albany Street, Boston, MA, 02118, USA 4. Institute of Human Genetics, University of Bonn, Bonn, Germany 3. Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands 5. Developmental Genetics Department, Max Planck Institute for Molecular Genetics, Berlin, Germany 13. Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University, Freiburg, Germany 19. Faculty of Biology, Albert-Ludwigs-University, Freiburg, Germany 6. Renal Division, University Hospital Freiburg, Freiburg, Germany 14. BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University, Freiburg, Germany 15. Department of Neonatology, Children’s Hospital, University of Bonn, Bonn, Germany 16. Egyptian Group for Orphan Renal Diseases (EGORD), Cairo, Egypt 7. Department of Pediatrics, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt 17. Institute of Mother and Child Healthcare of Serbia, Belgrade, Serbia 8. Medical Faculty, University of Belgrade, Belgrade, Serbia 9. Department of Surgery, Kuwait University, Safat, Kuwait 10. Department of Genetics, Yale University School of Medicine, New Haven, CT, USA 18. Yale Center for Mendelian Genomics, Yale University School of Medicine, New Haven, CT, USA 20. Howard Hughes Medical Institute, Chevy Chase, MD, USA 11. Department of Pediatric Nephrology, University Children’s Hospital, Skopje, Macedonia
- 刊物类别:Biomedical and Life Sciences
- 刊物主题:Biomedicine
Human Genetics Molecular Medicine Internal Medicine Metabolic Diseases
- 出版者:Springer Berlin / Heidelberg
- ISSN:1432-1203
文摘
Congenital anomalies of the kidney and urinary tract (CAKUT) account for 40-0?% of chronic kidney disease that manifests in the first two decades of life. Thus far, 31 monogenic causes of isolated CAKUT have been described, explaining ~12?% of cases. To identify additional CAKUT-causing genes, we performed whole-exome sequencing followed by a genetic burden analysis in 26 genetically unsolved families with CAKUT. We identified two heterozygous mutations in SRGAP1 in 2 unrelated families. SRGAP1 is a small GTPase-activating protein in the SLIT2–ROBO2 signaling pathway, which is essential for development of the metanephric kidney. We then examined the pathway-derived candidate gene SLIT2 for mutations in cohort of 749 individuals with CAKUT and we identified 3 unrelated individuals with heterozygous mutations. The clinical phenotypes of individuals with mutations in SLIT2 or SRGAP1 were cystic dysplastic kidneys, unilateral renal agenesis, and duplicated collecting system. We show that SRGAP1 is expressed in early mouse nephrogenic mesenchyme and that it is coexpressed with ROBO2 in SIX2-positive nephron progenitor cells of the cap mesenchyme in developing rat kidney. We demonstrate that the newly identified mutations in SRGAP1 lead to an augmented inhibition of RAC1 in cultured human embryonic kidney cells and that the SLIT2 mutations compromise the ability of the SLIT2 ligand to inhibit cell migration. Thus, we report on two novel candidate genes for causing monogenic isolated CAKUT in humans.
| |
NGLC 2004-2010.National Geological Library of China All Rights Reserved.
Add:29 Xueyuan Rd,Haidian District,Beijing,PRC. Mail Add: 8324 mailbox 100083
For exchange or info please contact us via email.
| |