Progressive nephropathy associated with mitochondrial tRNA gene mutation

BackgroundThe prevalence of isolated hearing loss (HL) associated with the m.3243A>G mutation is unknown. The aim of this study was to assess the frequency and heteroplasmy level of the m.3243A>G mutation in a large group of Polish patients with postlingual bilateral sensorineural HL of unidentified cause.Methodology/Principal FindingsA molecular search was undertaken in the archival blood DNA of 1482 unrelated patients with isolated HL that had begun at ages between 5 and 40 years. Maternal relatives of the probands were subsequently investigated and all carriers underwent audiological tests. The m.3243A>G mutation was found in 16 of 1482 probands (an incidence of 1.08%) and 18 family members. Of these 34 individuals, hearing impairment was detected in 29 patients and the mean onset of HL was at 26 years. Some 42% of the identified m.3243A>G carriers did not develop multisystem symptomatology over the following 10 years. Mean heteroplasmy level of m.3243A>G was lowest in blood at a level of 14% and highest in urine at 58%. These values were independent of the manifested clinical severity of the disease.ConclusionsA single m.3243A>G carrier can usually be found among each 100 individuals who have postlingual hearing loss of unknown cause. Urine samples are best for detecting the m.3243A>G mutation and diagnosing mitochondrially inherited hearing loss.

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“…There was no relation between kidney disease in the patients 9 and 16 (Table 3) and level of urine heteroplasmy [30].…”

Section: Resultsmentioning

confidence: 85%

Postlingual Hearing Loss as a Mitochondrial 3243A>G Mutation Phenotype

et al. 2012

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“…A point mutation in the mitochondrial tRNAleu (UUR) at position 3243 (A3243G) has been associated with focal and segmental glomerulosclerosis (FSGS) (Dinour et al 2004), an important cause of nephrotic syndrome in children and adolescents that frequently progresses to ESRD. This mutation causes mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, as well as maternally inherited diabetes and deafness.…”

Section: Evidence Of Mitochondrial Injury In Renal Diseasementioning

confidence: 99%

The Emerging Role of Mitochondrial Targeting in Kidney Disease

Eirin

Lerman

2016

Handbook of Experimental Pharmacology

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Renal disease affects millions of people worldwide, imposing an enormous financial burden for health-care systems. Recent evidence suggests that mitochondria play an important role in the pathogenesis of different forms of renal disease, including genetic defects, acute kidney injury, chronic kidney disease, aging, renal tumors, and transplant nephropathy. Renal mitochondrial abnormalities and dysfunction affect several cellular pathways, leading to increased oxidative stress, apoptosis, microvascular loss, and fibrosis, all of which compromise renal function. Over recent years, compounds that specifically target mitochondria have emerged as promising therapeutic options for patients with renal disease. Although the most compelling evidence is based on preclinical studies, several compounds are currently being tested in clinical trials. This chapter provides an overview of the involvement of mitochondrial dysfunction in renal disease and summarizes the current knowledge on mitochondria-targeted strategies to attenuate renal disease.

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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]. …”

Section: Mitochondrial Disorders and Proteinuriamentioning

confidence: 99%

Progress in Pathogenesis of Proteinuria

Zhang

Huang

2012

International Journal of Nephrology

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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.

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Progressive nephropathy associated with mitochondrial tRNA gene mutation

Cited by 26 publications

References 0 publications

Postlingual Hearing Loss as a Mitochondrial 3243A>G Mutation Phenotype

Postlingual Hearing Loss as a Mitochondrial 3243A>G Mutation Phenotype

The Emerging Role of Mitochondrial Targeting in Kidney Disease

Progress in Pathogenesis of Proteinuria

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