Universität zu Köln

Kohl, Stefan, Chen, Jing, Vivante, Asaf, Hwang, Daw-Yang, Shril, Shirlee, Dworschak, Gabriel C., Van der Ven, Amelie, Sanna-Cherchi, Simone, Bauer, Stuart B., Lee, Richard S., Soliman, Neveen A., Kehinde, Elijah O., Reutter, Heiko M., Tasic, Velibor ORCID: 0000-0002-3377-1245 and Hildebrandt, Friedhelm (2016). Targeted sequencing of 96 renal developmental microRNAs in 1213 individuals from 980 families with congenital anomalies of the kidney and urinary tract. Nephrol. Dial. Transplant., 31 (8). S. 1280 - 1284. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2385

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Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney diseases in children and young adults, accounting for similar to 50% of cases. These anomalies represent maldevelopment of the genitourinary system and can be genetically explained in only 10-16% of cases by mutations or by copy number variations in protein coding sequences. Knock-out mouse models, lacking components of the microRNA (miRNA) processing machinery (i.e. Dicer, Drosha, Dgcr8), exhibit kidney malformations resembling human CAKUT. Given the Dicer-null mouse phenotype, which implicates a central role for miRNAs gene regulation during kidney development, we hypothesized that miRNAs expressed during kidney development may cause CAKUT in humans if mutated. To evaluate this possibility we carried out Next-Generation sequencing of 96 stem-loop regions of 73 renal developmental miRNA genes in 1248 individuals with non-syndromic CAKUT from 980 families. We sequenced 96 stem-loop regions encoded by 73 miRNA genes that are expressed during kidney development in humans, mice and rats. Overall, we identified in 31/1213 individuals from 26 families with 17 different single nucleotide variants. Two variants did not segregate with the disease and hence were not causative. Thirteen variants were likely benign variants because they occurred in control populations and/or they affected nucleotides of weak evolutionary conservation. Two out of 1213 unrelated individuals had potentially pathogenic variants with unknown biologic relevance affecting miRNAs MIR19B1 and MIR99A. Our results indicate that mutations affecting mature microRNAs in individuals with CAKUT are rare and thus most likely not a common cause of CAKUT in humans.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kohl, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Chen, Jing UNSPECIFIED UNSPECIFIED UNSPECIFIED Vivante, Asaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Hwang, Daw-Yang UNSPECIFIED UNSPECIFIED UNSPECIFIED Shril, Shirlee UNSPECIFIED UNSPECIFIED UNSPECIFIED Dworschak, Gabriel C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Van der Ven, Amelie UNSPECIFIED UNSPECIFIED UNSPECIFIED Sanna-Cherchi, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauer, Stuart B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lee, Richard S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Soliman, Neveen A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kehinde, Elijah O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reutter, Heiko M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tasic, Velibor UNSPECIFIED orcid.org/0000-0002-3377-1245 UNSPECIFIED Hildebrandt, Friedhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-267644
DOI:	10.1093/ndt/gfv447
Journal or Publication Title:	Nephrol. Dial. Transplant.
Volume:	31
Number:	8
Page Range:	S. 1280 - 1284
Date:	2016
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2385
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MUTATIONS; CAKUT; GENE; MALFORMATIONS; CILIOPATHY; MESENCHYME; DISEASE; HUMANS Multiple languages Transplantation; Urology & Nephrology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26764