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 language | English (US) |
|---|---|
| Pages (from-to) | 897-903 |
| Number of pages | 7 |
| Journal | Pediatric Nephrology |
| Volume | 26 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2011 |
| Externally published | Yes |
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Keywords
- Children
- Chronic kidney disease
- HNF1B
- PAX2
- Renal hypodysplasia
ASJC Scopus subject areas
- Nephrology
- Pediatrics, Perinatology, and Child Health
Cite this
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 journal › Article
}
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 -