Toggle Main Menu Toggle Search

Open Access padlockePrints

Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity

Lookup NU author(s): Professor John SayerORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we, performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering and identified 5 novel candidate genes (RBM48, FAM186B, PIASI, INCENP, and RCORI) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis, and allows identification of novel candidate genes.

Publication metadata

Author(s): Braun DA, Schueler M, Halbritter J, Gee HY, Porath JD, Lawson JA, Airik R, Shril S, Allen SJ, Stein D, Al Kindy A, Beck BB, Cengiz N, Moorani KN, Ozaltin F, Hashmi S, Sayer JA, Bockenhauer D, Soliman NA, Otto EA, Lifton RP, Hildebrandt F

Publication type: Article

Publication status: Published

Journal: Kidney International

Year: 2016

Volume: 89

Issue: 2

Pages: 468-475

Print publication date: 01/02/2016

Online publication date: 23/12/2015

Acceptance date: 20/08/2015

Date deposited: 04/05/2016

ISSN (print): 0085-2538

ISSN (electronic): 1523-1755

Publisher: Elsevier


DOI: 10.1038/ki.2015.317


Altmetrics provided by Altmetric


Funder referenceFunder name
ASN-NephCure Foundation grant
university endowments of the Faculty of Medicine (Stiftungsgelder Imhoff-Stifung)
06A101008Hacettepe University Infrastructure Project
2012-305608European Community's Seventh Framework Programme (FP7) (EURenOmics)
5U54HG006504National Institutes of Health
6-FY11-241March of Dimes Foundation
DK064614National Institutes of Health
DK1068306National Institutes of Health
DK1069274National Institutes of Health
DK099434National Institutes of Health