The epidemiology and mutation types of Leber’s hereditary optic neuropathy in Thailand

Figures & data

Figure 1. Flow diagram of patient selection process.

Table 1. PCR and sequencing primer of 3 common genetic tests.

Gene	mtDNA mutation	PCR Primers and sequencing primers (5’→3’)	Temperature (^oC)	Base position	Product size (bp)
PCR-RFLP
ND4	G11778A (before 2013)	F: CTC ATT ACT ATT CTG CCT AGC AAA CTC AAA CTA CGA ACG CAC TCA TGA TC R: GTA GGA GAG TGA TAT TTG ATC AGG	55	11728–11942	215
Bi-directional PCR, followed by Sanger sequencing technique
ND4	G11778A (since 2013)	F: CTC TAC CTC TCT ATA CTA ATC TCC CTA CAA ATC TCC TTA ATG CTA R: GTA GGA GAG TGA TAT TTG ATC AGG S: GTA GGA GAG TGA TAT TTG ATC AGG	55	11039–11942	904
ND6	T14484C	F: CAT CAC CTC AAC CCA AAA AGG C R: GGA TCA GGC AGG CGC CAA GGA GTG S: GGA TCA GGC AGG CGC CAA GGA GTG	55	14061–14873	813
ND1	G3460A	F: CCC GAT GGT GCA GCC GC R: GAG ATT GTT TGG GCT ACT GCT CGC S: TCC TCC CTG TAC GAA AGG AC	55	3007–3728	722

F: forward primer; R: reverse primer; S: sequencing primer.

Limitation of the study. Before 2013, PCR-RFLP was primarily done to detect the G11778A mutation, not the other LHON primary mutation types.

If it did not cause confusion, the S sequencing primer base position should be mentioned.

Table 2. Demographic data, by mtDNA mutation.

Mutation position in mtDNA	G11778A N = 209 patients	T14484C N = 20 patients
Gender
Male	191 (91.4%)	19 (95%)
Female	18 (8.6%)	1 (5%)
Age at onset	N = 79 patients	N = 10 patients
Median (years)	21.9	33.0
Range (years)	5.10, 59.93	15.80, 65.90

mt DNA: mitochondrial DNA.

Table 3. Comparison of visual progression of LHON patients with G11778A and T14484C mutations whose follow-up exceeded one year.

	Mutation
	11778 N = 79 eyes	14484 N = 10 eyes
	Median (IQR)	Median (IQR)	p Value^a
Follow-up period (years)	5.4 (2.8, 8.3)	2.6 (1.6, 4.5)	0.004
BCVA (logMAR) at first visit^b	1.6 (1.2, 2.3)	1.7 (1.0, 2.3)	0.115
BCVA (logMAR) at last visit	1.6 (1.3, 2.3)	0.5 (0.2, 1.8)	0.004
Difference of BCVA between first and last visit (logMAR)	0.0 (−0.3, 0.2)	−0.65 (−1.5, −0.2)	0.001

*Mann–Whitney U test (significance, p < 0.05).

^bBCVA within 6 months of onset.

BCVA: best-corrected visual acuity; IQR, interquartile range.

Table 4. Generalised estimating equation (GEE) analysis of correlation between final BCVA and other variables.

Variables	Co-efficiency	Standard error	95% CI	P value
Male gender	1.255	0.333	0.602 to 1.908	<0.001
G11778A mutation	1.016	0.297	0.434 to 1.598	0.001
Age	0.033	0.011	0.010 to 0.055	0.004
BCVA (logMAR) at first visit	0.014	0.135	−0.250 to 0.278	0.918

BCVA: best-corrected visual acuity.

Data availability statement

The data that support the findings of this study are available from the corresponding author, NC, upon reasonable request.