1. Variability in phenotype induced by the podocin variant R229Q plus a single pathogenic mutation.
- Author
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Phelan, Paul J., Hall, Gentzon, Wigfall, Delbert, Foreman, John, Nagaraj, Shashi, Malone, Andrew F., Winn, Michelle P., Howell, David N., and Gbadegesin, Rasheed
- Subjects
NEPHROTIC syndrome ,GENETIC mutation ,IMMUNOSUPPRESSIVE agents ,GENETICS - Abstract
Background: Mutations in podocin (NPHS2) are the most common cause of childhood onset autosomal recessive steroid-resistant nephrotic syndrome (SRNS). The disease is characterized by early-onset proteinuria, resistance to immunosuppressive therapy and rapid progression to end-stage renal disease. Compound heterozygous changes involving the podocin variant R229Q combined with another pathogenic mutation have been associated with a mild phenotype with disease onset often in adulthood. Methods: We screened 19 families with early-onset SRNS for mutations in NPHS2 and WT1 and identified four disease-causing mutations (three in NPHS2 and one in WT1) prior to planned whole-exome sequencing. Results: We describe two families with three individuals presenting in childhood who are compound heterozygous for R229Q and one other pathogenic NPHS2 mutation, either L327F or A297V. One child presented at age 4 years (A297V plus R229Q) and the other two at age 13 (L327F plus R229Q), one with steadily deteriorating renal function. Conclusions: These cases highlight the phenotypic variability associated with the NPHS2 R229Q variant plus pathogenic mutation. Individuals may present with early aggressive disease. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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