Universität zu Köln

Vivante, Asaf, Hwang, Daw-Yang, Kohl, Stefan, Chen, Jing, Shril, Shirlee, Schulz, Julian, van der Ven, Annelle, Daouk, Ghaleb, Soliman, Neveen A., Kumar, Aravind Selvin, Senguttuvan, Prabha, Kehinde, Elijah O., Tasic, Velibor ORCID: 0000-0002-3377-1245 and Hildebrandt, Friedhelm (2017). Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract. J. Am. Soc. Nephrol., 28 (1). S. 69 - 76. WASHINGTON: AMER SOC NEPHROLOGY. ISSN 1533-3450

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Abstract

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease-causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1. Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease-causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology-based diagnosis and improved clinical management.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vivante, Asaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Hwang, Daw-Yang UNSPECIFIED UNSPECIFIED UNSPECIFIED Kohl, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Chen, Jing UNSPECIFIED UNSPECIFIED UNSPECIFIED Shril, Shirlee UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulz, Julian UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Ven, Annelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Daouk, Ghaleb UNSPECIFIED UNSPECIFIED UNSPECIFIED Soliman, Neveen A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kumar, Aravind Selvin UNSPECIFIED UNSPECIFIED UNSPECIFIED Senguttuvan, Prabha UNSPECIFIED UNSPECIFIED UNSPECIFIED Kehinde, Elijah O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tasic, Velibor UNSPECIFIED orcid.org/0000-0002-3377-1245 UNSPECIFIED Hildebrandt, Friedhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-243663
DOI:	10.1681/ASN.2015080962
Journal or Publication Title:	J. Am. Soc. Nephrol.
Volume:	28
Number:	1
Page Range:	S. 69 - 76
Date:	2017
Publisher:	AMER SOC NEPHROLOGY
Place of Publication:	WASHINGTON
ISSN:	1533-3450
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CLINICAL PRESENTATION; PRIMARY HYPEROXALURIA; RECESSIVE MUTATIONS; WOLFRAM-SYNDROME; GENE; DISEASE; ABNORMALITIES; MALFORMATIONS; CILIOPATHIES; CYSTINOSIS Multiple languages Urology & Nephrology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24366