Progressive nephropathy associated with mitochondrial tRNA gene mutation

Department of Nephrology and Hypertension, The Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Clinical nephrology (Impact Factor: 1.13). 09/2004; 62(2):149-54. DOI: 10.5414/CNP62149
Source: PubMed

ABSTRACT Mitochondrial DNA plays a crucial role in oxidative production of energy. Thus, defects in mitochondrial DNA can affect virtually all organ systems. The point mutation A --> G at position 3243 in the mitochondrial tRNAleu(UUR) gene is the cause of several distinct types of mitochondrial cytopathy and several clinical phenotypes, including encephalomyopathy with lactic acidosis and stroke-like episodes and maternally inherited diabetes and deafness. This mutation has been recently described also in association with kidney disease, mainly focal and segmental glomerulosclerosis. At present, little is known about the prevalence of this mitochondrial nephropathy, its clinical course and the pathogenesis of glomerular damage. We describe 2 unrelated patients, who presented with proteinuria and progressed to end-stage renal failure. Other clinical features were short stature, severe headache, hearing loss, diabetes mellitus and hypertrophic cardiomyopathy. The main histological finding was an increased number of abnormal mitochondria in tubular cells and podocytes. Analysis of mitochondrial DNA from leukocytes and urine sediment revealed heteroplasmy for the A3243G mutation in tRNAleu(UUR) gene in both patients. Recognition of the characteristic clinical and histological features of the mitochondrial A3243G mutation-associated glomerulopathy will enable correct diagnosis and better management of a disease which is likely to be underdiagnosed.

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    • "Thus, defects in mitochondrial DNA can affect virtually all organ systems. Mitochondrial DNA mutations have been recently described also in association with kidney disease, mainly focal and segmental glomerulosclerosis [101]. "
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    ABSTRACT: Aims. Proteinuria not only is a sign of kidney damage, but also is involved in the progression of renal diseases as an independent pathologic factor. Clinically, glomerular proteinuria is most commonly observed, which relates to structural and functional anomalies in the glomerular filtration barrier. The aim of this paper was to describe the pathogenesis of glomerular proteinuria. Data Sources. Articles on glomerular proteinuria retrieved from Pubmed and MEDLINE in the recent 5 years were reviewed. Results. The new understanding of the roles of glomerular endothelial cells and the glomerular basement membrane (GBM) in the pathogenesis of glomerular proteinuria was gained. The close relationships of slit diaphragm (SD) molecules such as nephrin, podocin, CD2-associated protein (CD2AP), a-actinin-4, transient receptor potential cation channel 6 (TRPC6), Densin and membrane-associated guanylate kinase inverted 1 (MAGI-1), α3β1 integrin, WT1, phospholipase C epsilon-1 (PLCE1), Lmx1b, and MYH9, and mitochondrial disorders and circulating factors in the pathogenesis of glomerular proteinuria were also gradually discovered. Conclusion. Renal proteinuria is a manifestation of glomerular filtration barrier dysfunction. Not only glomerular endothelial cells and GBM, but also the glomerular podocytes and their SDs play an important role in the pathogenesis of glomerular proteinuria.
    05/2012; 2012(6):314251. DOI:10.1155/2012/314251
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    ABSTRACT: During the last decade, there has been a progressive accumulation of reports that connect the identification of specific mitochondrial tRNA gene mutations to severe disorders in human. As a result, mitochondrial tRNA genes and their products have emerged as novel and essential molecular markers for wide biochemical and genetic screenings among different human populations. So far, 139 pathogenic and 243 polymorphic mt tRNA mutations have been described and they have become the foreground of numerous case reports. Given the complexity of mitochondrial genetics and biochemistry, the clinical manifestations of mitochondrial disorders are extremely heterogeneous. They range from lesions of single tissues or structures to more severe impairments including myopathies, encephalomyopathies, cardiomyopathies, or complex multisystem syndromes. Moreover, the exact mechanisms by which biochemical cascades can be dramatically affected by mitochondrial tRNA mutations still remain uncharacterized. However and regardless of the vast amount of information that daily emerges, only few efforts have been carried out to systematically record all the mitochondrial tRNA-associated pathogenic mutations or polymorphisms. In this report, we summarize all the clinical phenotypes associated with mitochondrial tRNA pathogenic mutations that have been reported so far. In a next step we describe in detail all the pathogenic and polymorphic mutations that have been recorded so far and we categorize them per tRNA species and per associated disease. Finally, we discuss the impact of the frequency of mitochondrial tRNA mutations in general population surveys and we preview any relevant implications on the essential functional integrity of mitochondrial biochemical pathways.
    RNA biology 01/2007; 4(1):38-66. DOI:10.4161/rna.4.1.4548 · 4.97 Impact Factor
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    ABSTRACT: Mitochondrial defects play an important role in the pathogenesis of tubular syndromes, interstitial nephritis, focal and segmental glomerulosclerosis and diabetic nephropathy. The role of mitochondria in the pathogenesis of nephrotoxicity and kidney carcinogenesis is also discussed.
    01/2008: pages 161-187;
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