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

Pediatric Nephrology, Children's Hospital at Montefiore, Bronx, NY, USA.
Pediatric Nephrology (Impact Factor: 2.86). 03/2011; 26(6):897-903. DOI: 10.1007/s00467-011-1826-9
Source: PubMed


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.

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Available from: Simone Sanna-Cherchi, Jan 08, 2014
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    • "Microdeletions on chromosome 17q12 encompassing the hepatocyte nuclear factor 1β (HNF1β) have recently been characterized as an important cause of prenatally hyperechogenic kidneys, renal aplasia and renal hypodysplasia, which represent an important cause of chronic renal failure among children [1,2]. The following case expands the diverse spectrum of disorders associated with 17q12 microdeletions and reveals a hypothetical link with membranous nephropathy (MN), a common and often unaccounted cause of nephrotic syndrome in the adult population. "
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