Renal manifestations of genetic mitochondrial disease

Figures & data

Figure 1 Mitochondrial genome with the positions of mutations associated with a kidney phenotype. A schematic of the circular 16,569 base pair human mitochondrial genome is shown with the position of 13 protein-coding mitochondrial genes (ND1, ND2, CO1, CO2, ATP8, ATP6, CO3, ND3, ND4L, ND4, ND5, ND6, CYTB), two ribosomal ribonucleic acid (RNA) molecules (RNR1, RNR2) and the noncoding D-loop, depicted as labeled boxes on the interior of the circle. The position of the 22 mitochondrial transfer RNAs (tRNAs) is shown with the solid-gray boxes with the single-letter amino acid designation shown for the respective tRNA. The position of the mitochondrial transfer deoxyribonucleic acid (mtDNA) single-base mutations are shown with a solid-bold line on the interior of the circle connected to a light line indicating the base position of the mutation. Large mitochondrial DNA deletions are represented by bold lines labeled 1–8 on the exterior of the circle phenotype.

Table 1 Mitochondrial DNA mutations associated with a kidney phenotype

	Mutation	Gene	Renal phenotype	References
Mitochondrial DNA point mutations
	m.G586A	mt-tRNA^Phe	TIN	^Citation21
	m.A608G	mt-tRNA^Phe	TIN	^Citation20
	m.G3242A	mt-tRNA^Leu	Renal failure, RTA type 4	^Citation80,Citation81
	m.3243	mt-tRNA^Leu	FSGS	^Citation12^–^Citation14,Citation23^–^Citation26, ^Citation28,Citation29,Citation31^–^Citation35,Citation82
	m.3243	mt-tRNA^Leu	TIN	^Citation11,Citation12
	m.A4269G	mt-tRNA^Ile	FSGS	^Citation17
	m.A5656G	aNoncoding	TIN	^Citation22
	m.A5728G	mt-tRNA^Asn	FSGS	^Citation18
	m.A5843G	mt-tRNA^Tyr	FSGS	^Citation19
	m.12425delA	ND5	Glomerulocystic disease, renal failure	^Citation36
Figure 1 label	Deletion size	Deletion location	Renal phenotype	References
Mitochondrial DNA deletions
1	6,000 base pairs	∼6,000–12,000	Proximal tubulopathy	^Citation45
2	7,500 base pairs	∼6,100–13,600	FSGS, RTA	^Citation42
3	8,800 base pairs	∼6,800–15,600	Distal tubulopathy	^Citation39
4	7,315 base pairs	7,325–14,639	Proximal tubulopathy, TIN	^Citation46
5	5,700 base pairs	∼8,400–14,100	Proximal tubulopathy	^Citation43
6	4,977 base pairs	8,469–13,447	Proximal tubulopathy	^Citation44,Citation47
7	2,800 base pairs	∼10,000–12,800	Proximal tubulopathy, TIN	^Citation40
8	2,608 base pairs	10,598–13,206	TIN	^Citation41

Note:

a Single noncoding base between mt-tRNA^Ala and mt-tRNA^Asn.

Abbreviations: DNA, deoxyribonucleic acid; mt-tRNA, mitochondrial transfer ribonucleic acid; TIN, tubulointerstitial nephritis; FSGS, focal segmental glomerulosclerosis; RTA, renal tubular acidosis; Phe, phenylalanine; Leu, leucine; Ile, isoleucine; Tyr, tyrosine; Ala, alanine; ND5, NADH dehydrogenase 5.

Table 2 Nuclear genes encoding mitochondrial proteins associated with a kidney phenotype

Gene	Position	Renal phenotype	References
Coenzyme Q10 biosynthesis
PDSS2	Chromosome 6q21	Nephrotic syndrome	^Citation55
COQ2	Chromosome 4q21.23	Nephrotic syndrome	^Citation51^–^Citation54
COQ6	Chromosome 14q24.3	Nephrotic syndrome	^Citation56
COQ9	Chromosome 16q21	Renal tubulopathy	^Citation50
Mitochondrial protein translation
SARS2	Chromosome 19q13.2	Progressive renal failure, distal tubulopathy	^Citation60,Citation61
MRPS22	Chromosome 3q23	Renal tubulopathy	^Citation63
TSFM	Chromosome 12q14.1	Renal tubulopathy	^Citation64
Posttranslational modification of mitochondrial proteins
XPNPEP3	Chromosome 22q13.2	Interstitial fibrosis	^Citation65
Respiratory chain assembly and function
BCS1L	Chromosome 2q35	Proximal tubulopathy, TIN	^Citation68
SURF1	Chromosome 9q34.2	RTA	^Citation69
COX10	Chromosome 17p12	Proximal tubulopathy	^Citation71
TMEM70	Chromosome 8q21.11	Proximal RTA	^Citation70
Mitochondrial DNA depletion
MPV17	Chromosome 2p23.3	Renal failure	^Citation79
C10orf2	Chromosome 10q24.31	Proximal tubulopathy	^Citation72
SUCLA2	Chromosome 13q14.2	Methylmalonic aciduria	^Citation73,Citation74
SUCLG1	Chromosome 2p11.2	Methylmalonic aciduria	^Citation75
RRM2B	Chromosome 8q22.3	Proximal tubulopathy	^Citation76,Citation77
DGUOK	Chromosome 2p13.1	Cystathioninuria	^Citation78

Abbreviations: DNA, deoxyribonucleic acid; TIN, tubulointerstitial nephritis; RTA, renal tubular acidosis.

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