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Low prevalence of NPHS2 mutations in African American children with steroid-resistant nephrotic syndrome

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Abstract

In African American (AA) children, focal segmental glomerulosclerosis (FSGS) is the leading cause of nephrotic syndrome (NS). It has been shown that AA children suffer from FSGS and steroid-resistant nephrotic syndrome (SRNS) at a higher frequency and with a more severe renal outcome in comparison with Caucasian children. Previous mutation analysis of large cohorts revealed that a high percentage of childhood SRNS is monogenic and that mutations in podocin (NPHS2) and Wilms’ tumor gene 1 (WT1) account for approximately 30% of SRNS in children. To test whether AA children with SRNS have a similar or a higher mutation rate, we performed mutation analysis of NPHS2 and WT1 in a cohort of AA children with SRNS. Direct sequencing was carried out for all exons of NPHS2 and for exons 8 and 9 of WT1. We ascertained 18 children of AA descent in whom renal biopsy findings showed FSGS in 13 patients (72%) and minimal-change disease in five patients (28%). In both NPHS2 and WT1, no disease-causing mutations were detected. Our data strongly suggest that in AA children with SRNS, the frequency of NPHS2 mutations is much lower than in large cohorts of pediatric SRNS patients in the general population. Knowledge of mutation rate of NPHS2 in different populations of SRNS patients facilitates the physician in planning a suitable genetic screening strategy for patients.

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Acknowledgments

We thank the patients and their parents for participation in this study.

We thank I. Roberti (Livingston, NJ), A. Torres, (Kalamazoo, MI), C. Hanevold (Augusta, GA), C. Kashtan (Minneapolis, MN), and J. Hopcian (Ann Arbor, MI) for their contribution of materials and clinical data from patients. FH is the Frederick G.L. Huetwell professor and Doris Duke Distinguished Clinical Scientist and is supported by grants from the NIH (P50-DK039255, R01-DK076683), the Smokler Foundation, and the Thrasher Research Fund.

Disclosure

The authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, MI, USA

    Gil Chernin, Saskia F. Heeringa, Rasheed Gbadegesin, Jinhong Liu, Bernward G. Hinkes, Christopher N. Vlangos, Virginia Vega-Warner & Friedhelm Hildebrandt

  2. Departments of Pediatrics and of Human Genetics and Howard Hughes Medical Institute, University of Michigan Health System, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI, 48109-5646, USA

    Friedhelm Hildebrandt

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  1. Gil Chernin
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  2. Saskia F. Heeringa
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  3. Rasheed Gbadegesin
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  5. Bernward G. Hinkes
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  6. Christopher N. Vlangos
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Correspondence to Friedhelm Hildebrandt.

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Supplementary Table 1

Innocuous SNPs in African American children with SRNS (DOC 33 kb)

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Chernin, G., Heeringa, S.F., Gbadegesin, R. et al. Low prevalence of NPHS2 mutations in African American children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 23, 1455–1460 (2008). https://doi.org/10.1007/s00467-008-0861-7

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