Pediatric Nephrology

, Volume 26, Issue 6, pp 897–903 | Cite as

HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort

  • Rosemary Thomas
  • Simone Sanna-Cherchi
  • Bradley A. Warady
  • Susan L. Furth
  • Frederick J. Kaskel
  • Ali G. GharaviEmail author
Original Article


Malformations of the kidney and lower urinary tract are the most frequent cause of end-stage renal disease in children. Mutations in HNF1Β and PAX2 commonly cause syndromic urinary tract malformation. We searched for mutations in HNF1Β and PAX2 in North American children with renal aplasia and hypodysplasia (RHD) enrolled in the Chronic Kidney Disease in Children Cohort Study (CKiD). We identified seven mutations in this multiethnic cohort (10% of patients). In HNF1Β, we identified a nonsense (p.R181X), a missense (p.S148L), and a frameshift (Y352fsX352) mutation, and one whole gene deletion. In PAX2, we identified one splice site (IVS4-1G>T), one missense (p.G24E), and one frameshift (G24fsX28) mutation. All mutations occurred in Caucasians, accounting for 14% of disease in this subgroup. The absence of mutations in other ethnicities is likely due to the limited sample size. There were no differences in clinical parameters (age, baseline eGFR, blood pressure, body mass index, progression) between patients with or without HNF1B and PAX2 mutations. A significant proportion of North American Caucasian patients with RHD carry mutations in HNF1Β or PAX2 genes. These patients should be evaluated for complications (e.g., diabetes for HNF1Β mutations, colobomas for PAX2) and referred for genetic counseling.


HNF1B PAX2 Renal hypodysplasia Chronic kidney disease Children 



We thank the patients for their participation in this study. We thank Catarina Quinzii and Michio Hirano at The H. Houston Merritt Center for Neuromuscular and Mitochondrial Disorders at Columbia University for assistance with MLPA. This study was supported by 1R01DK080099 (AGG). Rosemary Thomas is supported by the T32 NIH training grant. Simone Sanna-Cherchi is supported by the American Heart Association Scientist Development Grant (0930151N) and the American Society of Nephrology Career Development Grant. Data in this manuscript were collected by the Chronic Kidney Disease in Children prospective cohort study (CKiD) with clinical coordinating centers (Principal Investigators) at the Children’s Mercy Hospital and the University of Missouri, Kansas City (Bradley Warady, MD) and the Children’s Hospital of Philadelphia (Susan Furth, MD, PhD), the central laboratory (Principal Investigator) at the Department of Pediatrics, University of Rochester Medical Center (George Schwartz, MD), and the data coordinating center (Principal Investigator) at the Johns Hopkins Bloomberg School of Public Health (Alvaro Muñoz, PhD). The CKiD is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01 DK066143, U01 DK066174, U01 DK082194, U01 DK066116). The CKiD website is located at

Supplementary material

467_2011_1826_MOESM1_ESM.doc (52 kb)
Supplementary Table 1 Prediction of pathogenicity via publicly available programs. (DOC 52 kb)
467_2011_1826_MOESM2_ESM.doc (94 kb)
Supplementary Table 2 Previously annotated SNPs found in the CKiD cohort. (DOC 94 kb)
467_2011_1826_MOESM3_ESM.doc (108 kb)
Supplementary Table 3 New variants HNF1B and PAX2. (DOC 107 kb)
467_2011_1826_MOESM4_ESM.doc (66 kb)
Supplemental Table 4 Clinical parameters of patients with and without mutations. (DOC 66 kb)
467_2011_1826_MOESM5_ESM.doc (282 kb)
Supplementary Fig. 1 Whole gene deletion of HNF1B (DOC 20.7 mb)
467_2011_1826_MOESM6_ESM.doc (962 kb)
Supplementary Fig. 2 Conservations among species for variants in PAX2 (DOC 1.08 mb)


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Copyright information

© IPNA 2011

Authors and Affiliations

  • Rosemary Thomas
    • 1
  • Simone Sanna-Cherchi
    • 2
  • Bradley A. Warady
    • 3
  • Susan L. Furth
    • 4
  • Frederick J. Kaskel
    • 1
  • Ali G. Gharavi
    • 2
    • 5
    Email author
  1. 1.Pediatric NephrologyChildren’s Hospital at MontefioreBronxUSA
  2. 2.NephrologyColumbia UniversityNew YorkUSA
  3. 3.Pediatric NephrologyChildren’s Mercy HospitalKansas CityUSA
  4. 4.Pediatric NephrologyChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  5. 5.Division of Nephrology, Department of Medicine, College of Physicians and SurgeonsColumbia UniversityNew YorkUSA

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