Survey of human mitochondrial diseases using new genomic/proteomic tools

Table 1 Selected mutations associated with human mitochondrial disorders

Disorder	Affected protein	DNA change	Protein change	Evolutionary conservation	Structural environment
LHON	ND4	G11778A	R340H	Absolute	N/A
	ND1	G3460A	A52T	Slight	N/A
	ND6	T14484C	M64V	Moderate	N/A
		G14459A	A72V	High	N/A
Leigh syndrome	ATP6	T8993G	L156R	Absolute	Subunit interface
	PDHA1	C892G	R263G	Slight	Near active site
	SURF1	G385A	G124E	Absolute	N/A
		T751C	I246T	High	Predicted β-sheet
	SDHA	C1684T	R554W	High	Surface-exposed
MNGIE	TP	G1419A	G145R	High	Near active site
		G1443A	G153S	Absolute	Near active site
		A2744G	K222S	Absolute	Near active site
		A3371	E289A	Absolute	Notin active site
Deafness-dystonia	DDP1	T151del (1 nt)	Truncation - see text	High	N/A
		A183del (10 nt)	Truncation - see text	High	NA
		C198G	C66W	Absolute	N/A
Iron-storage	ABCB7	ATT → ATG	I400M	High	Predicted tight turn
HSP	Paraplegin	784del (2 nt)	60% truncated	High	N/A
		2228ins (1 nt = A)	7.2% Truncated	Moderate	N/A

ABCB7, ATP-binding cassette, subfamily B, member 7; ATP4, adenosine triphosphate synthase subunit 4 (ATP6 - subunit 6); DDP1, deafness-dystonia peptide 1, del, deletion; HSP, hereditary spastic paraplegia; ins, insertion; LHON, Leber's hereditary optic neuropathy; MNGIE, mitochondrial neurogastrointestinal encephalomyopathy; N/A, not available; ND, NADH dehydrogenase; ND1 ... NDn, ND subunits 1 ... nt, nucleotide; PDHA1, pyruvate dehydrogenase subunit E1α; SDHA, succinate dehydrogenase subunit A; SURF1, surfeit locus protein 1; TP, thymidine phosphorylase.

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