Gee, Heon Yung ORCID: 0000-0002-8741-6177, Otto, Edgar A., Hurd, Toby W., Ashraf, Shazia, Chaki, Moumita, Cluckey, Andrew, Vega-Warner, Virginia, Saisawat, Pawaree, Diaz, Katrina A., Fang, Humphrey, Kohl, Stefan, Allen, Susan J., Airik, Rannar, Zhou, Weibin, Ramaswami, Gokul, Janssen, Sabine, Fu, Clementine, Innis, Jamie L., Weber, Stefanie, Vester, Udo, Davis, Erica E., Katsanis, Nicholas ORCID: 0000-0002-2480-0171, Fathy, Hanan M., Jeck, Nikola, Klaus, Gunther, Nayir, Ahmet, Rahim, Khawla A., Al Attrach, Ibrahim, Al Hassoun, Ibrahim, Ozturk, Savas ORCID: 0000-0002-0961-3810, Drozdz, Dorota, Helmchen, Udo, O'Toole, John F., Attanasio, Massimo ORCID: 0000-0002-1278-3650, Lewis, Richard A., Nuernberg, Gudrun, Nuernberg, Peter, Washburn, Joseph, MacDonald, James, Innis, Jeffrey W., Levy, Shawn ORCID: 0000-0002-1369-5740 and Hildebrandt, Friedhelm (2014). Whole-exome resequencing distinguishes cystic kidney diseases from phenocopies in renal ciliopathies. Kidney Int., 85 (4). S. 880 - 888. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1755

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Abstract

Rare single-gene disorders cause chronic disease. However, half of the 6000 recessive single gene causes of disease are still unknown. Because recessive disease genes can illuminate, at least in part, disease pathomechanism, their identification offers direct opportunities for improved clinical management and potentially treatment. Rare diseases comprise the majority of chronic kidney disease (CKD) in children but are notoriously difficult to diagnose. Whole-exome resequencing facilitates identification of recessive disease genes. However, its utility is impeded by the large number of genetic variants detected. We here overcome this limitation by combining homozygosity mapping with whole-exome resequencing in 10 sib pairs with a nephronophthisis-related ciliopathy, which represents the most frequent genetic cause of CKD in the first three decades of life. In 7 of 10 sibships with a histologic or ultrasonographic diagnosis of nephronophthisis-related ciliopathy, we detect the causative gene. In six sibships, we identify mutations of known nephronophthisis-related ciliopathy genes, while in two additional sibships we found mutations in the known CKD-causing genes SLC4A1 and AGXT as phenocopies of nephronophthisis-related ciliopathy. Thus, whole-exome resequencing establishes an efficient, noninvasive approach towards early detection and causation-based diagnosis of rare kidney diseases. This approach can be extended to other rare recessive disorders, thereby

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gee, Heon YungUNSPECIFIEDorcid.org/0000-0002-8741-6177UNSPECIFIED
Otto, Edgar A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hurd, Toby W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ashraf, ShaziaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chaki, MoumitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cluckey, AndrewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vega-Warner, VirginiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saisawat, PawareeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diaz, Katrina A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fang, HumphreyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kohl, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Allen, Susan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Airik, RannarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhou, WeibinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramaswami, GokulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janssen, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fu, ClementineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Innis, Jamie L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vester, UdoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davis, Erica E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Katsanis, NicholasUNSPECIFIEDorcid.org/0000-0002-2480-0171UNSPECIFIED
Fathy, Hanan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jeck, NikolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klaus, GuntherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nayir, AhmetUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rahim, Khawla A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Al Attrach, IbrahimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Al Hassoun, IbrahimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ozturk, SavasUNSPECIFIEDorcid.org/0000-0002-0961-3810UNSPECIFIED
Drozdz, DorotaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helmchen, UdoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
O'Toole, John F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Attanasio, MassimoUNSPECIFIEDorcid.org/0000-0002-1278-3650UNSPECIFIED
Lewis, Richard A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, GudrunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Washburn, JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
MacDonald, JamesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Innis, Jeffrey W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levy, ShawnUNSPECIFIEDorcid.org/0000-0002-1369-5740UNSPECIFIED
Hildebrandt, FriedhelmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-442728
DOI: 10.1038/ki.2013.450
Journal or Publication Title: Kidney Int.
Volume: 85
Number: 4
Page Range: S. 880 - 888
Date: 2014
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1523-1755
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CENTROSOMAL PROTEIN; JOUBERT-SYNDROME; LINKAGE ANALYSIS; DOMAIN PROTEIN; NEPHRONOPHTHISIS; MUTATIONS; GENE; CAPTURE; CILIARY; INTERACTSMultiple languages
Urology & NephrologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/44272

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