Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/52359
Title: GENETIC EPISTASIS BETWEEN TRPC6 MUTATION AND NEPHRIN POLYMORPHISMS IN HEREDITARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS
Authors: SUN ZIJIN
Keywords: TRPC6, FSGS, Nephrin, Polymorphisms, Calcium channel
Issue Date: 14-Aug-2013
Source: SUN ZIJIN (2013-08-14). GENETIC EPISTASIS BETWEEN TRPC6 MUTATION AND NEPHRIN POLYMORPHISMS IN HEREDITARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS. ScholarBank@NUS Repository.
Abstract: The mechanism that individuals with TRPC6 mutations have variable penetrance is unknown. We describe here a family where six members had a novel TRPC6 p.R68W (c.202C>T) mutation. One healthy carrier donated a kidney to her sister who had renal failure and they had no proteinuria 19 years after transplant. We found two synonymous NPHS1 polymorphisms, c.294C>T and c.2289C>T, that segregated with disease in this family. By using patch-clamp electrophysiology, our result showed that p.R68W mutation enhances surface expression and current amplitudes of TRPC6 channels. In addition, wild-type nephrin suppresses TRPC6 currents but this ability is lost in the presence of NPHS1 c.294C>T polymorphism, which decreases nephrin mRNA stability and expression. We also found that cells representing the donor had lower TRPC6 currents than cells representing the recipient. Our work suggests interactions between TRPC6 and NPHS1 variants which can account for the variable penetrance in TRPC6 mutations and the absence of recurrence in the graft.
URI: http://scholarbank.nus.edu.sg/handle/10635/52359
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