Copy number variation analysis identifies novel CAKUT candidate genes in children with a solitary functioning kidney

Kidney International
Rik WestlandSimone Sanna-Cherchi

Abstract

Copy number variations associate with different developmental phenotypes and represent a major cause of congenital anomalies of the kidney and urinary tract (CAKUT). Because rare pathogenic copy number variations are often large and contain multiple genes, identification of the underlying genetic drivers has proven to be difficult. Here we studied the role of rare copy number variations in 80 patients from the KIMONO study cohort for which pathogenic mutations in three genes commonly implicated in CAKUT were excluded. In total, 13 known or novel genomic imbalances in 11 of 80 patients were absent or extremely rare in 23,362 population controls. To identify the most likely genetic drivers for the CAKUT phenotype underlying these rare copy number variations, we used a systematic in silico approach based on frequency in a large data set of controls, annotation with publicly available databases for developmental diseases, tolerance and haploinsufficiency scores, and gene expression profile in the developing kidney and urinary tract. Five novel candidate genes for CAKUT were identified that showed specific expression in the human and mouse developing urinary tract. Among these genes, DLG1 and KIF12 are likely novel susceptibility ge...Continue Reading

References

Jul 3, 2002·Nature Reviews. Genetics·Seppo Vainio, Yanfeng Lin
Aug 3, 2004·Pediatrics·UNKNOWN National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents
Feb 25, 2005·Journal of the American Society of Nephrology : JASN·Michal MrugLisa M Guay-Woodford
Apr 15, 2005·Journal of the American Society of Nephrology : JASN·Simone Sanna-CherchiAli G Gharavi
Sep 15, 2006·Journal of the American Society of Nephrology : JASN·Stefanie WeberRemi Salomon
Mar 17, 2007·Science·Jonathan SebatMichael Wigler
Apr 17, 2007·Development·Akiko Iizuka-KogoTakao Senda
Apr 18, 2007·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Simone Sanna-CherchiGian Marco Ghiggeri
May 17, 2007·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Elizabeth McPherson
Sep 20, 2007·Nature Reviews. Genetics·Andreas Schedl
Oct 10, 2007·American Journal of Human Genetics·Heather C MeffordChristine Bellanne-Chantelot
Nov 14, 2008·Journal of the American Society of Nephrology : JASN·Yimei GongPeter Igarashi
May 16, 2009·Journal of the American Society of Nephrology : JASN·Patricia L WengAli G Gharavi
Jun 19, 2009·Kidney International·Simone Sanna-CherchiGian Marco Ghiggeri
Jul 15, 2009·Nature Genetics·Steven C GreenwayChristine E Seidman
Dec 17, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Shazia AshrafFriedhelm Hildebrandt
Oct 27, 2010·PLoS Genetics·Ni HuangMatthew E Hurles
Nov 4, 2010·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Pauline Abou JaoudéPierre Cochat
Mar 2, 2011·Nature Reviews. Genetics·Can AlkanEvan E Eichler
Mar 8, 2011·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Rosemary ThomasAli G Gharavi
Jun 30, 2011·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Jérôme HarambatE Jane Tizard
Aug 16, 2011·Nature Genetics·Gregory M CooperEvan E Eichler
Feb 3, 2012·The British Journal of Dermatology·S A Wisniewski, W H Trzeciak
Feb 4, 2012·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Chunlin WangZhenshan Huang
Sep 14, 2012·The New England Journal of Medicine·Santhosh GirirajanEvan E Eichler
Oct 23, 2012·Clinical Journal of the American Society of Nephrology : CJASN·Elke WühlFranz Schaefer
Jan 16, 2013·Pediatrics·Rik WestlandMichiel F Schreuder
Feb 14, 2013·Acta Neuropathologica·David E ReussAndreas von Deimling
May 11, 2013·Journal of the American Society of Nephrology : JASN·Sun-Young AhnJeffrey H Miner
Jun 12, 2013·Current Opinion in Genetics & Development·Christelle Golzio, Nicholas Katsanis
Aug 31, 2013·PLoS Genetics·Slavé PetrovskiDavid B Goldstein
Dec 3, 2013·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Anna Materna-KirylukAnna Latos-Bielenska
Dec 29, 2013·Clinical Journal of the American Society of Nephrology : CJASN·Rik WestlandJoanna A E van Wijk
Jan 9, 2014·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Asaf VivanteFriedhelm Hildebrandt
Oct 1, 2012·Journal of Nephropathology·Jameela Kari
Oct 2, 2014·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Georgina CaruanaJohn F Bertram

❮ Previous
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Citations

Jun 5, 2016·Urology·Cinzia ChiaramonteGiuseppe Li Voti
Jan 26, 2017·The New England Journal of Medicine·Esther Lopez-RiveraSimone Sanna-Cherchi
Apr 12, 2017·International Journal of Molecular Sciences·Valentina P CaponeGiovanni Montini
Jan 11, 2018·Pediatric Research·Lena Sagi-DainShay Ben-Shachar
May 10, 2018·Obstetrics and Gynecology·Marva Moxey-Mims, Tonse N K Raju
Dec 21, 2018·Wiley Interdisciplinary Reviews. Developmental Biology·Ming S Tham, Ian M Smyth
Feb 9, 2019·Clinical and Experimental Nephrology·Qian XuNan Chen
Jun 2, 2017·Journal of the American Society of Nephrology : JASN·Laurence HeidetCécile Jeanpierre
Jan 9, 2018·Nature Reviews. Nephrology·Emily E GroopmanAli G Gharavi
Dec 15, 2019·Molecular Genetics & Genomic Medicine·Johanna WinbergAgneta Nordenskjöld
Apr 3, 2020·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Pierluigi Marzuillo, Cesare Polito
Oct 19, 2017·Journal of Nephrology·Jordan G NestorAli G Gharavi
Jun 15, 2019·Clinical Kidney Journal·Sanjay Jain, Feng Chen
Apr 22, 2020·Clinical Journal of the American Society of Nephrology : CJASN·Rik WestlandNine V A M Knoers
Jan 3, 2018·The Journal of Clinical Investigation·Simone Sanna-CherchiAli G Gharavi
Jul 3, 2018·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Silvia Ferrè, Peter Igarashi
May 31, 2017·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Michiel F Schreuder
May 9, 2019·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Melissa H Little, Catherine Quinlan
Dec 24, 2018·Nature Genetics·Miguel VerbitskySimone Sanna-Cherchi
May 21, 2020·Journal of Medical Genetics·Silvia Kalantari, Isabel Filges
Feb 19, 2021·Journal of the American Society of Nephrology : JASN·Miguel VerbitskyAli G Gharavi

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Methods Mentioned

BETA
dissection
PCR
genotyping

Software Mentioned

Ensembl
GenomeStudio Viewer
PennCNV
Exome Variant Server ( EVS )
KIMONO
Perl scripts
PLINK
GenomeStudio

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