2002
DOI: 10.1097/01.asn.0000019772.17954.f8
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Mitochondrial DNA Mutations in Focal Segmental Glomerulosclerosis Lesions

Abstract: ABSTRACT. Glomerular epithelial cells are primary pathogenic sites in focal segmental glomerulosclerosis (FGS) lesions. Glomerular epithelial cells are regarded as terminally differentiated cells that do not proliferate. These characteristics are also noted for neurons and muscular cells, which are major sites of mitochondrial DNA (mtDNA) mutation accumulation. Screening for mtDNA mutations was performed with renal biopsy specimens from patients with primary FGS and patients with IgA nephropathy (as subjects w… Show more

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Cited by 65 publications
(41 citation statements)
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“…For example, the ACTN4, IFN2, or TRPC6 genes are broadly expressed, but their mutations produce podocyte dysfunction and nephropathy (53)(54)(55). Similarly, mutations in some genes encoding mitochondrial respiratory chains produce podocyte dysfunction, while acquired mtDNA mutations have also been described in focal segmental glomerulosclerosis lesions (56,57). One can surmise that genetic mutations produce functional defects only in cells/organs lacking redundant or modifier pathways or in the setting of specific physiologic states or metabolic demands.…”
Section: Figurementioning
confidence: 99%
“…For example, the ACTN4, IFN2, or TRPC6 genes are broadly expressed, but their mutations produce podocyte dysfunction and nephropathy (53)(54)(55). Similarly, mutations in some genes encoding mitochondrial respiratory chains produce podocyte dysfunction, while acquired mtDNA mutations have also been described in focal segmental glomerulosclerosis lesions (56,57). One can surmise that genetic mutations produce functional defects only in cells/organs lacking redundant or modifier pathways or in the setting of specific physiologic states or metabolic demands.…”
Section: Figurementioning
confidence: 99%
“…While kidney disease due to mitochondrial point mutations has occasionally been reported in the absence of extrarenal features, 13,23 it more commonly occurs in the setting of MELAS syndrome 14,[24][25][26][27][28] or deafness, which usually occurs with diabetes. 11,12,26,[29][30][31][32][33][34][35] Point mutations that occur in a protein-coding region of mtDNA in association with a kidney phenotype are very rare. 36 A singlebase deletion in the complex I subunit NADH dehydrogenase 5, has been reported to occur in a single individual with glomerulocystic kidney disease and renal failure.…”
mentioning
confidence: 99%
“…The other positional candidates encode structural proteins (Pkb2 and Fgd4) or proteins that are involved in mitochondrial homeostasis (Dnm1l), cellular stress signaling, and DNA repair (Ube2v2, Prkdc, Mcm4, and Cebpd). Defects in these pathways have been implicated either in the development of chemotherapeutic cytotoxicity or in the pathogenesis of glomerulosclerosis (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(32)(33)(34), making these genes plausible candidates as DOXNPH. We now can proceed with systematic sequence and functional analysis of these remaining positional candidates to identify the susceptibility variant.…”
Section: Resultsmentioning
confidence: 99%