ArticleGenetics in medicine : official journal of the American College of Medical Genetics2022
Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06785558 (The Role of Urinary ATP in the Diagnosis, Treatment, and Follow-up of Children With Overactive Bladder), which is not on this map. Cited by 30 papers.
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30citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
What it found
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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.
The Role of Urinary ATP in the Diagnosis, Treatment, and Follow-up of Children With Overactive Bladder
Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- Personalized Medicine in Pediatric Urology: From Diagnosis to Individualized Risk Assessment.Medical sciences (Basel, Switzerland) · 2026Review
- Rare Biallelic CTU2 Variants in an Individual With CAKUT: Clinical Characterization and Minigene Splicing Analysis.Molecular genetics & genomic medicine · 2026Article
- Clinical impact of genetic testing in inherited kidney diseases.Clinical kidney journal · 2026Article
- CRONDEX: a web-based platform for exploring links between chromatin-related genes and neurodevelopmental disorders.Clinical epigenetics · 2026Article
- Identification of monogenic variants in steroid-resistant and steroid-sensitive nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2026Article
- Article
- Diagnostic Yield and Genotype-Phenotype Overlap in Pediatric Autism Spectrum Disorder Patients Using Whole-Exome Sequencing and Phenotype-Driven Variant Interpretation: A Single-Center Cohort Study.Children (Basel, Switzerland) · 2026Article
- Genetic testing in chronic kidney disease of uneXplained cause (CKDx): clinical insights and evolving diagnostic paradigms.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- From Genes to Malformations: Molecular Mechanisms Driving the Pathogenesis of Congenital Anomalies of the Kidney and Urinary Tract.International journal of molecular sciences · 2025Review
- Functional Characterization of a NovelGenes · 2025Article
- Exome Sequencing in Saudi Arabian Pediatric Kidney Disease Single-Center Cohort.Kidney international reports · 2025Article
- Trio exome sequencing identifies de novo variants in novel candidate genes in 19.62% of CAKUT families.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Article
- A de novo SALL4 mutation causes unilateral renal agenesis by misregulating genes involved in kidney development.Orphanet journal of rare diseases · 2025Article
- Extrarenal Clinical Features are Reported for Most Genes Implicated in Genetic Kidney Disease.Kidney international reports · 2025Article
- Genomics and multiomics in the age of precision medicine.Pediatric research · 2025Review
- Genetic Contributions to Lower Urinary Tract Dysfunction.American journal of medical genetics. Part A · 2025Article
- Genitourinary defects, anxiety and aggressive-like behavior and glucose metabolism disorders inFrontiers in cell and developmental biology · 2025Article
- Vitamin A Deficiency Disturbs Ret Expression and Induces Urinary Tract Developmental Abnormalities in Mice.American journal of nephrology · 2025Article
- Framework for standardized genetic testing recommendations for chronic kidney disease in Ontario.Genetics in medicine open · 2025Article
Corrections and comments
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Authors and funding
45 authors at 9 institutions in 7 countries.
Steve SeltzsamDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Chunyan WangDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Bixia ZhengDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Nina MannDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Dervla M ConnaughtonDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Chen-Han Wilfred WuDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA; Division of Genetics and Genomics, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Sophia SchneiderDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Luca SchierbaumDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Franziska KauseDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Caroline M KolvenbachDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Makiko NakayamaDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Rufeng DaiDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Isabel OttlewskiDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Ronen SchneiderDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Konstantin DeutschDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Florian BuergerDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Verena KlämbtDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Youying MaoDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Ana C Onuchic-WhitfordDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA; Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Camille Nicolas-FrankDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Kirollos YousefDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Dalia PantelDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA; Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
Ethan W LaiDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Daanya SalmanullahDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Amar J MajmundarDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Stuart B BauerDepartment of Urology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Nancy M RodigDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Michael J G SomersDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Avram Z TraumDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Deborah R SteinDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Ankana DagaDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Michelle A BaumDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Ghaleb H DaoukDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Velibor TasicMedical Faculty Skopje, University Children's Hospital, Skopje, North Macedonia.
Hazem S AwadPediatric Nephrology Department, Dubai Hospital, Dubai, United Arab Emirates.
Loai A EidPediatric Nephrology Department, Dubai Hospital, Dubai, United Arab Emirates.
Sherif El DesokyDepartment of Pediatrics, King Abdul Aziz University, Jeddah, Saudi Arabia; Pediatric Nephrology Center of Excellence, Department of Pediatrics, King Abdul Aziz University, Jeddah, Saudi Arabia.
Mohammed ShalabyDepartment of Pediatrics, King Abdul Aziz University, Jeddah, Saudi Arabia; Pediatric Nephrology Center of Excellence, Department of Pediatrics, King Abdul Aziz University, Jeddah, Saudi Arabia.
Jameela A KariDepartment of Pediatrics, King Abdul Aziz University, Jeddah, Saudi Arabia; Pediatric Nephrology Center of Excellence, Department of Pediatrics, King Abdul Aziz University, Jeddah, Saudi Arabia.
Hanan M FathyPediatric Nephrology Unit, University of Alexandria, Alexandria, Egypt.
Neveen A SolimanDepartment of Pediatrics, Center of Pediatric Nephrology and Transplantation, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt.
Shrikant M ManeDepartment of Genetics, Yale University School of Medicine, New Haven, CT.
Shirlee ShrilDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Michael A FergusonDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Friedhelm HildebrandtDivision of Nephrology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA. Electronic address: friedhelm.hildebrandt@childrens.harvard.edu.
Boston Children's Hospital · USHarvard University · USKing Abdul Aziz University Hospital · SADubai Hospital · AEAlexandria University · EGCairo University · EGHeidelberg University · DEPHI University Psychiatric Clinic - Skopje · MKYale 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
$102.9MRenal Physiology and Phenotyping CoreP30DK079310 · NIDDK · YALE UNIVERSITY · PI ARONSON, PETER S. · 2008 to 2022
$16.8MYale Center for Mendelian GenomicsUM1HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2016 to 2020
$14.8MTRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0MYale Center for Mendelian DisordersU54HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2012 to 2015
$11.0MThe Child Heath Research CenterK12HD052896 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Wendy K Chung · 2007 to 2026
$7.9MNovel genetics, pathobiology & therapy of nephronophthisis-related ciliopathiesR01DK068306 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HILDEBRANDT, FRIEDHELM · 2004 to 2022
$6.6MRESEARCH TRAINING IN PEDIATRIC NEPHROLOGYT32DK007726 · NIDDK · CHILDREN'S HOSPITAL BOSTON · PI BRISCOE, DAVID M. · 1994 to 2023
$5.9MIdentification and function of new genes causing childhood nephrotic syndromeR01DK076683 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HILDEBRANDT, FRIEDHELM · 2007 to 2021
$5.3MNew genes and pathomechanisms of congenital abnormalities of the kidney (CAKUT)R01DK088767 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HILDEBRANDT, FRIEDHELM · 2010 to 2019
$3.4MDelineation of pathogenic mechanisms of NOS1AP and TRIM8 mutations in monogenic SRNS/FSGS.K08DK125768 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI MAJMUNDAR, AMAR J · 2021 to 2025
$841kMutations in TBC1D8B as a potential new cause of nephrotic syndromeF32DK122766 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI ONUCHIC-WHITFORD, ANA CLAUDIA · 2019 to 2020
$148kNCATS NIH HHS UL1 TR001863NHGRI NIH HHS U54 HG006504NHGRI NIH HHS UM1 HG006504NICHD NIH HHS K12 HD052896NIDDK NIH HHS F32 DK122766NIDDK NIH HHS K08 DK125768NIDDK NIH HHS P30 DK079310NIDDK NIH HHS R01 DK068306NIDDK NIH HHS R01 DK076683NIDDK NIH HHS R01 DK088767NIDDK NIH HHS T32 DK007726NIGMS NIH HHS T32 GM007748
Abstract
purposeCongenital anomalies of the kidneys and urinary tract (CAKUT) constitute the leading cause of chronic kidney disease in children. In total, 174 monogenic causes of isolated or syndromic CAKUT are known. However, syndromic features may be overlooked when the initial clinical diagnosis of CAKUT is made. We hypothesized that the yield of a molecular genetic diagnosis by exome sequencing (ES) can be increased by applying reverse phenotyping, by re-examining the case for signs/symptoms of the suspected clinical syndrome that results from the genetic variant detected by ES.
methodsWe conducted ES in an international cohort of 731 unrelated families with CAKUT. We evaluated ES data for variants in 174 genes, in which variants are known to cause isolated or syndromic CAKUT. In cases in which ES suggested a previously unreported syndromic phenotype, we conducted reverse phenotyping.
resultsIn 83 of 731 (11.4%) families, we detected a likely CAKUT-causing genetic variant consistent with an isolated or syndromic CAKUT phenotype. In 19 of these 83 families (22.9%), reverse phenotyping yielded syndromic clinical findings, thereby strengthening the genotype-phenotype correlation.
conclusionWe conclude that employing reverse phenotyping in the evaluation of syndromic CAKUT genes by ES provides an important tool to facilitate molecular genetic diagnostics in CAKUT.
Indexed as
Urinary TractUrogenital AbnormalitiesAllelesExomeHumansKidneyVesico-Ureteral RefluxCongenital anomalies of the kidneys and urinary tract (CAKUT)Exome sequencingMonogenic disease causationRenal developmental gene
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Registered trials
NCT06785558ClinicalTrials.gov
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