Evidence map›Paper›PMID 36185583›Full record

ArticleEuropean urology open science2022

Copy Number Variation Analysis Facilitates Identification of Genetic Causation in Patients with Congenital Anomalies of the Kidney and Urinary Tract.

Chen-Han Wilfred Wu, Tze Y Lim, Chunyan Wang, Steve Seltzsam, Bixia Zheng, Luca Schierbaum, Sophia Schneider, Nina Mann, Dervla M Connaughton, Makiko Nakayama and 26 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European urology open science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Genetics of CAKUT.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors at 12 institutions in 6 countries.

Chen-Han Wilfred WuDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Tze Y LimDivision of Nephrology, Columbia University Irving Medical Center, New York, NY, USA.
Chunyan WangDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Steve SeltzsamDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Bixia ZhengDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Luca SchierbaumDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Sophia SchneiderDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Nina MannDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Dervla M ConnaughtonDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Makiko NakayamaDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Amelie T van der VenDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Rufeng DaiDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Caroline M KolvenbachDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Franziska KauseDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Isabel OttlewskiDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Natasa StajicDepartment of Pediatric Nephrology, Institute for Mother and Child Health Care, Belgrade, Serbia.
Neveen A SolimanDepartment of Pediatrics, Center of Pediatric Nephrology & Transplantation, Cairo University, Egyptian Group for Orphan Renal Diseases, Cairo, Egypt.
Jameela A KariDepartment of Pediatrics, King AbdulAziz University, Jeddah, Saudi Arabia.
Sherif El DesokyDepartment of Pediatrics, King AbdulAziz University, Jeddah, Saudi Arabia.
Hanan M FathyPediatric Nephrology Unit, University of Alexandria, Alexandria, Egypt.
Danko MilosevicDepartment of Pediatric Nephrology, University Hospital Center Zagreb, Zagreb, Croatia.
Daniel TurudicDepartment of Pediatric Nephrology, University Hospital Center Zagreb, Zagreb, Croatia.
Muna Al SaffarDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Hazem S AwadPediatric Nephrology Department, Dubai Hospital, Dubai, United Arab Emirates.
Loai A EidPediatric Nephrology Department, Dubai Hospital, Dubai, United Arab Emirates.
Aravind RamanathanEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Prabha SenguttuvanDepartment of Pediatric Nephrology, Dr. Mehta's Multi-Specialty Hospital, Chennai, India.
Shrikant M ManeDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Richard S LeeDepartment of Urology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Stuart B BauerDepartment of Urology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Weining LuRenal Section, Department of Medicine, Boston University Medical Center, Boston, MA, USA.
Alina C HilgerDepartment of Pediatric and Adolescent Medicine, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Velibor TasicMedical Faculty Skopje, University Children's Hospital, Skopje, Macedonia.
Shirlee ShrilDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Simone Sanna-CherchiDivision of Nephrology, Columbia University Irving Medical Center, New York, NY, USA.
Friedhelm HildebrandtDepartment of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Harvard University · USBoston Children's Hospital · USColumbia University Irving Medical Center · USDubai Hospital · AEKing Abdulaziz University · SAAlexandria University · EGCairo University · EGChildren's Clinical University Hospital · LVEunice Kennedy Shriver National Institute of Child Health and Human Development · USInstitute of Public Health of Serbia · RSUniversity Hospitals of Cleveland · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Renal Physiology and Phenotyping CoreP30DK079310 · NIDDK · YALE UNIVERSITY · PI SOMLO, STEFAN · 2008 to 2022
$16.8M
Molecular Pathogenesis of Vesicoureteral RefluxR01DK078226 · NIDDK · BOSTON MEDICAL CENTER · PI LU, WEINING · 2008 to 2018
$2.5M
New Therapeutic Leads for Proteinuric Kidney DiseasesR01DK133940 · NIDDK · BOSTON MEDICAL CENTER · PI LU, WEINING · 2022 to 2024
$790k
NCATS NIH HHS UL1 TR001863NIDDK NIH HHS P30 DK079310NIDDK NIH HHS R01 DK078226NIDDK NIH HHS R01 DK133940
6 · The paper itself

Abstract

Background: Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of chronic kidney disease among children and adults younger than 30 yr. In our previous study, whole-exome sequencing (WES) identified a known monogenic cause of isolated or syndromic CAKUT in 13% of families with CAKUT. However, WES has limitations and detection of copy number variations (CNV) is technically challenging, and CNVs causative of CAKUT have previously been detected in up to 16% of cases. Objective: To detect CNVs causing CAKUT in this WES cohort and increase the diagnostic yield. Design setting and participants: We performed a genome-wide single nucleotide polymorphism (SNP)-based CNV analysis on the same CAKUT cohort for whom WES was previously conducted. Outcome measurements and statistical analysis: We evaluated and classified the CNVs using previously published predefined criteria. Results and limitations: In a cohort of 170 CAKUT families, we detected a pathogenic CNV known to cause CAKUT in nine families (5.29%, 9/170). There were no competing variants on genome-wide CNV analysis or WES analysis. In addition, we identified novel likely pathogenic CNVs that may cause a CAKUT phenotype in three of the 170 families (1.76%). Conclusions: CNV analysis in this cohort of 170 CAKUT families previously examined via WES increased the rate of diagnosis of genetic causes of CAKUT from 13% on WES to 18% on WES + CNV analysis combined. We also identified three candidate loci that may potentially cause CAKUT. Patient summary: We conducted a genetics study on families with congenital anomalies of the kidney and urinary tract (CAKUT). We identified gene mutations that can explain CAKUT symptoms in 5.29% of the families, which increased the percentage of genetic causes of CAKUT to 18% from a previous study, so roughly one in five of our patients with CAKUT had a genetic cause. These analyses can help patients with CAKUT and their families in identifying a possible genetic cause.

Indexed as

BAF, B allele frequencyCAKUT, Congenital anomalies of the kidneys and urinary tractCNV, Copy number variationsCongenital anomalies of the kidney and urinary tractCopy number variationGD-CNV, Genomic disorders copy number variationIRB, Institutional review boardMonogenic disease causationRenal developmentalVesicoureteral refluxWES, Whole-exome sequencingWhole-exome sequencing

Identifiers

PMID36185583
PMCPMC9520493
OpenAlexW4294091125

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.