A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis

被引:840
作者
Winn, MP [1 ]
Conlon, PJ
Lynn, KL
Farrington, MK
Creazzo, T
Hawkins, AF
Daskalakis, N
Kwan, SY
Ebersviller, S
Burchette, JL
Pericak-Vance, MA
Howel, DN
Vance, JM
Rosenberg, PB
机构
[1] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27710 USA
[3] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA
[4] Beaumont Hosp, Dept Nephrol, Dublin, Ireland
[5] Christchurch Hosp, Dept Nephrol, Christchurch, New Zealand
[6] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA
[7] Durham VA Med Ctr, Durham, NC 27710 USA
关键词
D O I
10.1126/science.1106215
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Focal and segmental glomerulosclerosis (FSGS) is a kidney disorder of unknown etiology, and up to 20% of patients on dialysis have been diagnosed with it. Here we show that a large family with hereditary FSGS carries a missense mutation in the TRPC6 gene on chromosome 11q, encoding the ion-channel protein transient receptor potential cation channel 6 (TRPC6). The proline-to-glutamine substitution at position 112, which occurs in a highly conserved region of the protein, enhances TRPC6-mediated calcium signals in response to agonists such as angiotensin II and appears to alter the intracellular distribution of TRPC6 protein. Previous work has emphasized the importance of cytosketetal and structural proteins in proteinuric kidney diseases. Our findings suggest an alternative mechanism for the pathogenesis of glomerular disease.
引用
收藏
页码:1801 / 1804
页数:4
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