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

Research output: Contribution to journalArticle

Abstract

Malformations of the kidney and lower urinary tract are the most frequent cause of end-stage renal disease in children. Mutations in HNF1B and PAX2 commonly cause syndromic urinary tract malformation. We searched for mutations in HNF1B and PAX2 in North Americanchildren 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 HNF1B, 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 HNF1B or PAX2 genes. These patients should be evaluated for complications (e.g., diabetes for HNF1B mutations, colobomas for PAX2) and referred for genetic counseling.

Original languageEnglish (US)
Pages (from-to)897-903
Number of pages7
JournalPediatric Nephrology
Volume26
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

Fingerprint

Kidney
Mutation
Frameshift Mutation
Urinary Tract
Coloboma
Genetic Counseling
Gene Deletion
Diabetes Complications
Chronic Renal Insufficiency
Sample Size
Chronic Kidney Failure
Body Mass Index
Cohort Studies
Blood Pressure
Genes
Renal Adysplasia

Keywords

  • Children
  • Chronic kidney disease
  • HNF1B
  • PAX2
  • Renal hypodysplasia

ASJC Scopus subject areas

  • Nephrology
  • Pediatrics, Perinatology, and Child Health

Cite this

Thomas, R., Sanna-Cherchi, S., Warady, B. A., Furth, S. L., Kaskel, F. J., & Gharavi, A. G. (2011). HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort. Pediatric Nephrology, 26(6), 897-903. https://doi.org/10.1007/s00467-011-1826-9

HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort. / Thomas, Rosemary; Sanna-Cherchi, Simone; Warady, Bradley A.; Furth, Susan L.; Kaskel, Frederick J.; Gharavi, Ali G.

In: Pediatric Nephrology, Vol. 26, No. 6, 06.2011, p. 897-903.

Research output: Contribution to journalArticle

Thomas, R, Sanna-Cherchi, S, Warady, BA, Furth, SL, Kaskel, FJ & Gharavi, AG 2011, 'HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort', Pediatric Nephrology, vol. 26, no. 6, pp. 897-903. https://doi.org/10.1007/s00467-011-1826-9
Thomas R, Sanna-Cherchi S, Warady BA, Furth SL, Kaskel FJ, Gharavi AG. HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort. Pediatric Nephrology. 2011 Jun;26(6):897-903. https://doi.org/10.1007/s00467-011-1826-9
Thomas, Rosemary ; Sanna-Cherchi, Simone ; Warady, Bradley A. ; Furth, Susan L. ; Kaskel, Frederick J. ; Gharavi, Ali G. / HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort. In: Pediatric Nephrology. 2011 ; Vol. 26, No. 6. pp. 897-903.
@article{2e5b8365bcc041fd82d18f4b9da6c28a,
title = "HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort",
abstract = "Malformations of the kidney and lower urinary tract are the most frequent cause of end-stage renal disease in children. Mutations in HNF1B and PAX2 commonly cause syndromic urinary tract malformation. We searched for mutations in HNF1B and PAX2 in North Americanchildren 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 HNF1B, 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 HNF1B or PAX2 genes. These patients should be evaluated for complications (e.g., diabetes for HNF1B mutations, colobomas for PAX2) and referred for genetic counseling.",
keywords = "Children, Chronic kidney disease, HNF1B, PAX2, Renal hypodysplasia",
author = "Rosemary Thomas and Simone Sanna-Cherchi and Warady, {Bradley A.} and Furth, {Susan L.} and Kaskel, {Frederick J.} and Gharavi, {Ali G.}",
year = "2011",
month = "6",
doi = "10.1007/s00467-011-1826-9",
language = "English (US)",
volume = "26",
pages = "897--903",
journal = "Pediatric Nephrology",
issn = "0931-041X",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort

AU - Thomas, Rosemary

AU - Sanna-Cherchi, Simone

AU - Warady, Bradley A.

AU - Furth, Susan L.

AU - Kaskel, Frederick J.

AU - Gharavi, Ali G.

PY - 2011/6

Y1 - 2011/6

N2 - Malformations of the kidney and lower urinary tract are the most frequent cause of end-stage renal disease in children. Mutations in HNF1B and PAX2 commonly cause syndromic urinary tract malformation. We searched for mutations in HNF1B and PAX2 in North Americanchildren 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 HNF1B, 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 HNF1B or PAX2 genes. These patients should be evaluated for complications (e.g., diabetes for HNF1B mutations, colobomas for PAX2) and referred for genetic counseling.

AB - Malformations of the kidney and lower urinary tract are the most frequent cause of end-stage renal disease in children. Mutations in HNF1B and PAX2 commonly cause syndromic urinary tract malformation. We searched for mutations in HNF1B and PAX2 in North Americanchildren 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 HNF1B, 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 HNF1B or PAX2 genes. These patients should be evaluated for complications (e.g., diabetes for HNF1B mutations, colobomas for PAX2) and referred for genetic counseling.

KW - Children

KW - Chronic kidney disease

KW - HNF1B

KW - PAX2

KW - Renal hypodysplasia

UR - http://www.scopus.com/inward/record.url?scp=79959953210&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959953210&partnerID=8YFLogxK

U2 - 10.1007/s00467-011-1826-9

DO - 10.1007/s00467-011-1826-9

M3 - Article

C2 - 21380624

AN - SCOPUS:79959953210

VL - 26

SP - 897

EP - 903

JO - Pediatric Nephrology

JF - Pediatric Nephrology

SN - 0931-041X

IS - 6

ER -