Fratter et al. Page 1

Table e-1 : Clinical features, muscle histochemistry and molecular genetic findings in 33 patients with PEO1 mutations.

Patient / Clinical features / Onset/age /

Affected

Relatives

/ Skeletal muscle histochemistry / Multiple
mtDNA deletions / cDNA
change / Amino acid
change / Twinkle protein
domain / Published Reference / Allele
frequency (95% CI)
1 / PEO, ptosis, hearing loss / 60y/78y / Sister, mother, grandmother, maternal aunt / numerous
COX-ve, few RRF / +SB
+ LR-PCR / c.907C>T / p.R303W / Primase / 33 / 0.00 - 1.52%
2 / PEO, ptosis / 50y/60y / Mother / 3% COX-ve / + LR-PCR / c.907C>T / p.R303W / Primase / 33 / 0.00 - 1.52%
3 / PEO, ptosis, proximal myopathy, fatigue, hypothyroidism / 60y/69y / Mother / few COX-ve
RRF / +SB
+LR-PCR / c.908G>A / p.R303Q / Primase / 19 / 0.00 - 1.43%
4 / PEO, ptosis / <63y/69y / Mother & sibling / n.d. / +SB
+ LR-PCR / c.908G>A / p.R303Q / Primase / 19 / 0.00 - 1.43%
5.1 / PEO, diplopia, muscle pain, proximal myopathy, dysphagia, mild LVH / 51y/65y / Sister / single COX-deficient fiber / - SB
- LR-PCR / c.1001G>A / p.R334Q / Primase / 33 / 0.00 - 1.60%
5.2 / Fatigue, LBP, CTS, migraine,
mild LVH / 41y/43y / Mother & aunt / n.d. / n.d. / c.1001G>A / p.R334Q / Primase / 33 / 0.00 - 1.60%
5.3 / PEO, ptosis, fatigue, blurred vision, dysphagia, tinnitus, unsteadiness, hypothyroidism, DM, constipation / 48/58y / Cousins / n.d. / n.d. / c.1001G>A / p.R334Q / Primase / 33 / 0.00 - 1.60%
5.4 / PEO, ptosis, proximal myopathy, fatigue, cramps, cataract, mild LVH, prolonged QT / 58y/67y / Sister / n.d. / n.d. / c.1001G>A / p.R334Q / Primase / 33 / 0.00 - 1.60%
6 / PEO, proximal myopathy, dysphagia, cataract, visual impairment / 49y/60y / Mother / 5% COX-ve / -SB,
+ LR-PCR / c.1001G>A / p.R334Q / Primase / 33 / 0.00 - 1.60%
7 / PEO, ptosis, fatigue, epilepsy / 25y/56y / Mother &
grandfather / several COX-ve / + LR-PCR / c.1061G>C / p.R354P / Linker / 9 / 0.00 - 1.63%
8.1 / PEO, ptosis, fatigue, blurred vision / 48y/53y / Siblings / 2-3% COX-ve / +SB
+LR PCR / c.1061G>C / p.R354P / Linker / 9 / 0.00 - 1.63%
8.2 / PEO, ptosis, dysphagia, proximal myopathy, mild LVH, DM / 50y/78y / 2 daughters / n.d. / n.d. / c.1061G>C / p.R354P / Linker / 9 / 0.00 - 1.63%
8.3 / Ptosis, blurred vision / 47y/50y / Mother & sister / n.d. / n.d. / c.1061G>C / p.R354P / Linker / 9 / 0.00 - 1.63%
9 / PEO, ptosis / 65y/71y / Mother / 6% COX-ve, numerous RRF / n.d. / c.1070G>C / p.R357P / Linker / 38 / 0.00 - 1.60%
10 / PEO, ptosis / 47y/52y / Mother & sister / 2-3% COX-ve, few RRF / +SB
+LR PCR / c.1075G>A / p.A359T / Linker / 9 / 0.00 - 1.41%
11 / PEO, ptosis, proximal myopathy / n.d./70y / Sister & niece / 9% COX-ve,
3% RRF / -SB
+LR PCR / c.1075G>A / p.A359T / Linker / 9 / 0.00 - 1.41%
12 / PEO, ptosis / 49y/52y / None / several COX-ve, RRF / +LR-PCR / c.1075G>A / p.A359T / Linker / 9 / 0.00 - 1.41%
13 / PEO, ptosis / 8y/58y / Grandmother mother, uncle / n.d. / n.d. / c.1084G>C / p.A362P / Linker / Novel / 0.00 - 1.60%
14 / PEO, ptosis, incomplete RBBB / 50y/72y / Daughter (45y) / 2-3% COX-ve / +LR-PCR / c.1088G>T / p.W363L / Linker / Novel / 0.00 - 1.60%
15 / PEO, ptosis, ovarian failure / 10y/19y / None / >5% COX-ve, several RRF / +SB
+LR-PCR / c.1109T>G / p.F370C / Linker / Novel / 0.00 - 1.35%
16 / PEO, fatigue, lethargy, migraine / 30y/35y / None / 10% COX-ve,
1% RRF / +LR PCR / c.1121G>A / p.R374Q / Linker / 9 / 0.00 - 1.62%
17 / PEO / 10y/32y / n.d. / 10% COX-ve,
1% RRF / n.d. / c.1121G>A / p.R374Q / Linker / 9 / 0.00 - 1.62%
18 / PEO, migraine / 30y/49y / Mother, 1 brother,1 sister, maternal uncle and grandfather / mitochondrial changes including 2 RRF / -SB
LR-PCR n.d. / c.1121G>A / p.R374Q / Linker / 9 / 0.00 - 1.62%
19.1 / PEO, blurred vision, muscle pain, lethargy, fatigue, dysphagia, irritable bowel, LBBB / 45y/66y / Brother / 5% COX-ve, 1%RRF / +LR-PCR / c.1142T>C / p.L381P / N-terminal of helicase / 9 / 0.00 - 1.63%
19.2 / PEO, ptosis, myalgias, fatigue, proximal myopathy / 41y/57y / 2 siblings / n.d. / n.d. / c.1142T>C / p.L381P / N-terminal of helicase / 9 / 0.00 - 1.63%
19.3 / PEO, ptosis, fatigue / 51y/67y / 2 siblings / n.d. / n.d. / c.1142T>C / p.L381P / N-terminal of helicase / 9 / 0.00 - 1.63%
20 / PEO, ptosis hearing loss, fatigue / 46y/55y / Mother & grandmother / several COX-ve, few RRF / + SB
+ LR-PCR / c.1374G>T / p.Q458H / between Walker A/B motif / Novel / 0.00 - 1.34%
21 / PEO, ptosis, visual impairment / 22y/53y / 2 brothers & paternal uncle / several COX-ve some RRF / +SB
+LR-PCR / c.1374G>T / p.Q458H / between Walker A/B motif / Novel / 0.00 - 1.34%
22 / PEO, ptosis / 44y/59y / Father & brother / some COX-ve, few RRF / +SB
+LR-PCR / c.1374G>T / p.Q458H / between Walker A/B motif / Novel / 0.00 - 1.34%
23 / PEO, ptosis, myalgia, fatigue, sensory peripheral neuropathy / 24y/31y / n.d. / several COX-ve / +SB
+LR-PCR / c.1378G>C / p.A460P / between Walker A/B motif / Novel / 0.00 - 1.58%
24 / PEO, cataracts / 50y/68y / Mother, sister & daughter / n.d. / n.d. / c.1379C>G / p.A460G / Between Walker A/B motif / Novel / 0.00 - 1.58%
25 / PEO, ptosis, fatigue, weakness, AIDS, psychiatric symptoms, hearing loss, diarrhoea / 33y/44y / Father & brother / n.d. / + LR-PCR in father / c.1424C>A / p.A475D / between Walker A/B motif / Novel / 0.00 - 1.39%
26 / PEO, ptosis, double vision, proximal myopathy, neck flexion weakness / 27y/50y / None / 22% COX-ve, 5%RRF / +SB
+ LR-PCR / c.1435G>A / p.E479K / between Walker A/B motif / 18 / 0.00 - 1.35%

SB = Southern blot; LR-PCR = long-range PCR; COX = cytochrome c oxidase; RRF = ragged-red fiber; n.d. = not determined; - = not present; + = present; LVH = left ventricular hypertrophy; LBP = low back pain; CTS = carpet tunnel syndrome; DM = diabetes mellitus; BBB = bundle branch block