Renal manifestations of primary mitochondrial disorders

Finsterer, Josef; Scorza, Fúlvio A.

doi:10.3892/br.2017.892

Cited by 65 publications

(60 citation statements)

References 83 publications

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“…FSGS is a recognized but uncommon manifestation of the mt.3243A>G mutation, although the actual end-stage renal failure (ESRF) appears rare [7][8][9]. The twin patients we describe developed similar manifestations but had a notable difference in disease trajectory.…”

Section: Discussionmentioning

confidence: 69%

“…This apparent relationship between mt.3243A>G heteroplasmy and renal replacement therapy could be confounded by the decline in leucocyte mt.3243 heteroplasmy with age [7]. Two groups have previously proposed methods of correcting for this [1,10].…”

Section: Discussionmentioning

confidence: 99%

“…In the kidneys, the mt.3243A>G may manifest as focal segmental glomerulosclerosis (FSGS) or, rarely, end-stage kidney disease [7][8][9]. To date, there has not been a recognized association between mt.3243A>Grelated kidney disease and peripheral leucocyte heteroplasmy.…”

Section: Introductionmentioning

confidence: 99%

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Increased Peripheral Blood Heteroplasmy of the mt.3243A>G Mutation Is Associated with Earlier End-Stage Kidney Disease: A Case Report and Review of the Literature

Shand

Potter

Pilmore

et al. 2020

Nephron

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The mitochondrial DNA mutation mt.3243A>G is most commonly associated with maternally inherited diabetes and deafness (MIM 52,000), but it has protean phenotypes including renal disease due to focal segmental glomerulosclerosis. We describe monozygotic twins who both harboured this mutation and developed ESRD. Although otherwise genetically identical, the twins differed in their peripheral blood leucocyte levels of circulating mt.3243A>G heteroplasmy: 20 versus 10%, when assessed at 42 years of age. The twin with the higher heteroplasmy load developed end-stage kidney disease 15 years earlier than her sister. A review of the published literature supports a relationship between heteroplasmy level and the age at the development of the end stage of renal failure in patients with mt.3243A>G-related kidney disease.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

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Increased Peripheral Blood Heteroplasmy of the mt.3243A>G Mutation Is Associated with Earlier End-Stage Kidney Disease: A Case Report and Review of the Literature

Shand

Potter

Pilmore

et al. 2020

Nephron

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“…Although mitochondrial diseases most often have a muscular or nervous phenotype, they can affect any organ. Primary renal manifestations in mitochondrial disorders include tubulopathy, interstitial nephritis, glomerular pathology and cystic disease . Kidney pathology is more frequently reported in children than in adult .…”

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confidence: 99%

“…Kidney pathology is more frequently reported in children than in adult . The most common mitochondrial DNA (mtDNA) defects reported with a kidney phenotype during adulthood are the mutation m.3243A>G in the tRNA ‐leu gene associated to myopathy encephalopathy lactic acidosis and stroke (MELAS) syndrome and mtDNA large scale deletions associated to Kearns‐Sayre Syndrome . Rare single case reports have described supplemental point mutations, most of them involving tRNA genes .…”

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confidence: 99%

Adult onset tubulo‐interstitial nephropathy in MT‐ND5‐related phenotypes

et al. 2020

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Kidney is a highly adenosine triphosphate dependent organ in human body. Healthy and functional mitochondria are essential for normal kidney function. Clinical and genetic variability are the hallmarks of mitochondrial disorders. We report here the involvement of two MT‐ND5 pathogenic variants encoding for ND5 subunit of respiratory chain complex I, the m.13513G>A and the m.13514A>G, in adult‐onset kidney disease in three unrelated patients. The first patient had myopathy encephalopathy lactic acidosis and stroke syndrome, left ventricular hypertrophy with Wolff‐Parkinson‐White syndrome and tubulo‐interstitial kidney disease. The second presented Leber hereditary optic neuropathy associated with tubulo‐interstitial kidney disease. The third presented with an isolated chronic tubulo‐interstitial kidney disease. These mutations have never been associated with adulthood mitochondrial nephropathy. These case reports highlight the importance to consider mitochondrial dysfunction in tubulo‐interstitial kidney disease.

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The role of novel COQ8B mutations in glomerulopathy and related kidney defects

AbuMaziad

Thaker

Tomasiak

et al. 2020

American J of Med Genetics Pt A

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Background and Objectives Glomerulopathies affect kidney glomeruli and can lead to end‐stage renal disease if untreated. Clinical and experimental evidence have identified numerous (>20) genetic mutations in the mitochondrial coenzyme Q8B protein (COQ8B) primarily associated with nephrotic syndrome. Yet, little else is understood about COQ8B activity in renal pathogenesis and its role in mitochondrial dysfunction. We identified additional novel COQ8B mutations in a glomerulopathy patient and aimed to define the potential structural and functional defects of COQ8B mutations. Design, Setting, Participants, and Measurements Whole exome sequencing was performed on a Hispanic female presenting with proteinuria. Novel mutations in the COQ8B gene were identified. The effects of mutation on protein function, mitochondrial morphology, and disease progression were investigated by histopathology, transmission electron microscopy, homology modeling, and in silico structural analysis. Results We have characterized the pathophysiology of novel COQ8B mutations, compound heterozygous for two alterations c.1037T>G (p.I346S), and c.1560G>A (p.W520X), in the progression of proteinuria in a Hispanic female. Histopathology revealed defects in podocyte structure and mitochondrial morphology. In silico and computation analyses highlight possible structural origins of COQ8B dysfunction in the presence of mutations. Conclusions Novel mutations in COQ8B present promising biomarkers for the early detection and therapeutic targeting of mitochondrial glomerulopathy. Insights from structural modeling suggest roles of mutation‐dependent alterations in COQ8B allosteric regulation, protein folding, or stability in renal pathogenesis.

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Renal manifestations of primary mitochondrial disorders

Cited by 65 publications

References 83 publications

Increased Peripheral Blood Heteroplasmy of the mt.3243A>G Mutation Is Associated with Earlier End-Stage Kidney Disease: A Case Report and Review of the Literature

Increased Peripheral Blood Heteroplasmy of the mt.3243A>G Mutation Is Associated with Earlier End-Stage Kidney Disease: A Case Report and Review of the Literature

Adult onset tubulo‐interstitial nephropathy in MT‐ND5‐related phenotypes

The role of novel COQ8B mutations in glomerulopathy and related kidney defects

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Renal manifestations of primary mitochondrial disorders

Cited by 65 publications

References 83 publications

Increased Peripheral Blood Heteroplasmy of the mt.3243A&#x3e;G Mutation Is Associated with Earlier End-Stage Kidney Disease: A Case Report and Review of the Literature

Increased Peripheral Blood Heteroplasmy of the mt.3243A&#x3e;G Mutation Is Associated with Earlier End-Stage Kidney Disease: A Case Report and Review of the Literature

Adult onset tubulo‐interstitial nephropathy in MT‐ND5‐related phenotypes

The role of novel COQ8B mutations in glomerulopathy and related kidney defects

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Product

Resources

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Increased Peripheral Blood Heteroplasmy of the mt.3243A>G Mutation Is Associated with Earlier End-Stage Kidney Disease: A Case Report and Review of the Literature

Increased Peripheral Blood Heteroplasmy of the mt.3243A>G Mutation Is Associated with Earlier End-Stage Kidney Disease: A Case Report and Review of the Literature