Publication:
Whole-exome resequencing distinguishes cystic kidney diseases from phenocopies in renal ciliopathies

Loading...
Thumbnail Image
Date
2014-04-01T00:00:00Z
Authors
Authors
Gee, Heon Yung
Otto, Edgar A.
Hurd, Toby W.
Ashraf, Shazia
Chaki, Moumita
Cluckey, Andrew
Vega-Warner, Virginia
Saisawat, Pawaree
Diaz, Katrina A.
Fang, Humphrey
Journal Title
Journal ISSN
Volume Title
Publisher
Research Projects
Organizational Units
Journal Issue
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
Description
Keywords
kidney
Citation
Gee H. Y. , Otto E. A. , Hurd T. W. , Ashraf S., Chaki M., Cluckey A., Vega-Warner V., Saisawat P., Diaz K. A. , Fang H., et al., -Whole-exome resequencing distinguishes cystic kidney diseases from phenocopies in renal ciliopathies-, KIDNEY INTERNATIONAL, cilt.85, ss.880-887, 2014
Sustainable Development Goals