Pediatric Nephrology

, Volume 26, Issue 6, pp 897–903

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. Gharavi
Original Article

DOI: 10.1007/s00467-011-1826-9

Cite this article as:
Thomas, R., Sanna-Cherchi, S., Warady, B.A. et al. Pediatr Nephrol (2011) 26: 897. doi:10.1007/s00467-011-1826-9

Abstract

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.

Keywords

HNF1BPAX2Renal hypodysplasiaChronic kidney diseaseChildren

Supplementary material

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

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
  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