The roles of mitochondrial tRNA mutations in non-dystrophic myotonias

Figures & data

Figure 1. The secondary structure of nine mt-tRNA mutations, arrow indicated the mutation positions.

Figure 2. Sequence alignment of mt-tRNA^Leu(CUN) gene from 15 different species, arrow indicated the position 44, corresponding to the A12308G mutation.

Table 1. Molecular characterization of nine mt-tRNA mutations.

Gene	Mutation	Number of nucleotides in tRNA	Location in tRNA	Homoplasmy or Heteroplasmy	CI (%)	Watson-Crick base-pairing^a	Disease association	References
tRNA^Met	T4454C	58	T-loop	Homoplasmy	59.6		hypertension	Zhu et al. 2009
tRNA^Trp	A5568G	62	T-stem	Homoplasmy	82.6		hearing loss	Jacobs et al. 2005
tRNA^Cys	T5794C	33	anticodon stem	Homoplasmy	75.0		none	/
tRNA^Arg	A10438T	37	anticodon stem	Heteroplasmy	100		progressive encephalopathy	Uusimaa et al. 2004
tRNA^Arg	T10462C	66	acceptor arm	Homoplasmy	21.1	A-T↓	none	/
tRNA^Leu(CUN)	A12308G	44	variable region	Heteroplasmy	100	A-T↑	chronic progressive external ophthalmoplegia; stroke; cardiomyopathy; breast cancer risk	Zifa et al. 2008; Pulkes et al. 2000; Finnila et al. 2001; Covarrubias et al. 2008; van den Ouweland et al. 1992
tRNA^Thr	A15907G	22	D-stem	Homoplasmy	65.4		none	/
tRNA^Thr	A15924G	39	anticodon stem	Heteroplasmy	100	T-A↓	lethal infantile mitochondrial myopathy; fatal infantile respiratory enzyme deficiency	Brown et al. 1992; Yoon et al. 1991
tRNA^Thr	G15928A	43	anticodon stem	Heteroplasmy	100	C-G↓	multiple sclerosis; Parkinson's disease	Mayr-Wohlfart et al. 1996, 1997; Simon et al. 2000

^a Classic Watson–Crick (WC) base pair: created (↑) or disrupted (↓).

Table 2. The pathogenicity scoring system for A12308G, A15924G and G15928A mutations.

Scoring criteria	A12308G	Score/20	A15924G	Score/20	G15928A	Score/20	Classification
More than one independent report	Yes	2	Yes	2	Yes	2
Evolutionary conservation of the base pair	No changes	2	No changes	2	No changes	2	≤6 points: neutral polymorphisms;
Variant heteroplasmy	Yes	2	Yes	2	Yes	2
Segregation of the mutation with disease	Yes	2	Yes	2	Yes	2	7–10 points: possibly pathogenic;
Histochemical evidence of mitochondrial disease	No	0	No	0	No	0
Biochemical defect in complex I, III or IV	No	0	No	0	No	0
Evidence of mutation segregation with biochemical defect from single-fiber studies	Yes	5	No	0	No	0	11–13 points (not including evidence from single fiber, steady-state level or trans-mitochondrial cybrid studies): probably pathogenic
Mutant mt-tRNA steady-state level or evidence of pathogenicity in trans-mitochondrial cybrid studies	Weak evidence	2	Strong evidence	5	Weak evidence	2	≥11 points (including evidence from single fiber, steady-state level or trans-mitochondrial cybrid studies): definitely pathogenic
Maximum score	Definitely pathogenic	15	Definitely pathogenic	13	Possibly pathogenic	10

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Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.