Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups
Abstract
:1. Introduction
2. Results
2.1. Demographics and Genetic Analysis
2.2. Visual Acuity Data and Optic Nerve Head Structural Findings
2.3. Optic Nerve Function, Mitochondrial Variants, Heteroplasmy, and Haplogroup
2.4. Idebenone Treatment
3. Discussion
4. Materials and Methods
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | LHON-Affected | Asymptomatic Carriers | |
---|---|---|---|
Genetic mutation | 11778G>A | N = 9 | N = 13 |
3460G>A | N = 1 | N = 1 | |
14484T>C | N = 1 | N = 1 | |
DNAJC30 c.152A>G | N = 1 | ||
Parent country of birth: Ireland : Ukraine | N = 11 N = 1 | N = 15 N = 1 | |
Sex | Female/Male | 3/9 | 15/1 |
Age (years) | Median (IQR) | 27 (19–33) | 56 (42–61) |
Age onset | 19 (16–23.5) | ||
6 (2–14) |
Characteristics | LHON-Affected | Asymptomatic Carriers | ||
---|---|---|---|---|
Female (n) | 25% (3) | 94% (15) | ||
Age (years) | 27 (19, 33) | 56 (42, 61) | ||
Median (1st quartile, 3rd quartile) | ||||
Visual Acuity Median (1st quartile, 3rd quartile) | RE 1.8 (1.25, 2.25) | LE 1.8 (1.4, 2.1) | RE 0 (0, 0.1) | LE 0.05 (0, 0.2) |
Optic nerve fibre layer (RNFL) | ||||
Overall RNFL | −54 (−62, −23) | −50 (−62, −32) | 0.5 (−9, 13) | −2 (−16, 13) |
Temporal-RNFL | −48 (−38, −48) | −46 (−50, −45) | −2 (−9, 6) | −4 (−19, 4) |
TS-RNFL | −83 (−97, −25) | −77 (−91, −51) | −1 (−16, 14) | −11 (−24, 23) |
NS-RNFL | −44 (−54, −23) | −47 (−56, −18) | 6 (−19, 21) | 8 (−12, 19) |
Nasal-RNFL | −25 (−40, −10) | −24 (−39, −17) | 9 (−5, 18) | 3 (−18, 10) |
NI-RNFL | −48 (−73, −22) | −54 (−64, 2) | 4 (−19, 27) | 5 (−21, 17) |
TI-RNFL | −96 (−107, −41) | −89 (−111, −40) | 9 (−11, 20) | −15 (−45, 15) |
ID | Eye | VA | Global Nerve | ON-T | ON-TS | ON-NS | ON-N | ON-NI | ON-TI | |
---|---|---|---|---|---|---|---|---|---|---|
LHON | C1 | RE | 1.8 | −59 | −48 | −96 | −54 | −30 | −61 | −118 |
LE | 1.5 | −63 | −45 | −90 | −66 | −40 | −68 | −114 | ||
C2 | RE | 2.4 | −48 | −47 | −98 | −35 | −20 | −22 | −93 | |
LE | 2.1 | −45 | −57 | −91 | −35 | −17 | 2 | −88 | ||
C4 | RE | 2.7 | −74 | −56 | −99 | −77 | −53 | −70 | −131 | |
LE | 2.4 | −71 | −57 | −110 | −70 | −51 | −56 | −115 | ||
C6 | LE | 1 | −50 | −50 | −66 | −47 | −24 | −54 | −89 | |
C7 | RE | 1.8 | −64 | −48 | −69 | −52 | −56 | −94 | −99 | |
LE | 1.8 | −58 | −46 | −77 | −52 | −39 | −64 | −108 | ||
E1 | RE | 1 | 6 | 13 | −6 | −28 | −2 | 5 | 50 | |
LE | 1 | 11 | −2 | 15 | −18 | 10 | 34 | 40 | ||
C9 | RE | 1.6 | −61 | −44 | −97 | −54 | −35 | −80 | −103 | |
LE | 1.9 | −62 | −47 | −95 | −56 | −36 | −78 | −111 | ||
C10 | RE | 1.4 | −32 | −49 | −31 | −9 | −13 | −34 | −59 | |
LE | 1.3 | −32 | −46 | −51 | 2 | −24 | −30 | −40 | ||
E2 | RE | 1.5 | 9 | −21 | 36 | 63 | 9 | −21 | 12 | |
LE | 1.5 | 8 | −33 | 34 | 53 | −1 | 8 | 33 | ||
Asymptomatic | U1 | RE | 0 | 2 | 5 | −13 | −21 | 12 | 3 | 20 |
LE | 0.2 | 0 | −3 | −19 | −32 | 11 | 12 | 23 | ||
U2 | RE | 0 | −39 | −47 | −61 | −12 | −12 | −38 | −90 | |
LE | 0.2 | −42 | −47 | −67 | −17 | −21 | −35 | −87 | ||
U3 | RE | 0.1 | −7 | 10 | 1 | −13 | −16 | −27 | −2 | |
LE | 0.2 | −12 | 0 | −13 | 3 | −19 | −21 | −21 | ||
U4 | RE | 0.1 | 12 | −6 | −8 | 24 | 16 | 60 | −1 | |
LE | 0.2 | 13 | −10 | 22 | 54 | 1 | 50 | −8 | ||
U5 | RE | 0 | 23 | 13 | 1 | 38 | 26 | 42 | 22 | |
LE | 0 | 23 | 8 | 42 | 53 | 15 | 37 | 7 | ||
U6 | RE | 0.1 | −9 | −12 | −23 | −22 | 11 | 4 | −24 | |
LE | 0.1 | −11 | −4 | −23 | −1 | 1 | −21 | −36 | ||
U7 | RE | 0.1 | 4 | 2 | 13 | 9 | 5 | −20 | 14 | |
LE | 0 | 7 | −1 | 15 | 12 | 10 | 3 | 8 | ||
U8 | RE | 0.1 | 8 | −5 | 12 | 3 | 7 | 30 | 17 | |
LE | 2.4 | −26 | −52 | −45 | −11 | 5 | 15 | −70 | ||
U9 | RE | 0 | −1 | 8 | −3 | −29 | −3 | −19 | 32 | |
LE | 0 | 2 | −5 | −1 | −14 | 4 | 4 | 32 | ||
U10 | RE | 0 | 24 | 11 | 30 | 10 | 20 | 62 | 35 | |
LE | 0 | 24 | 5 | 34 | 12 | 22 | 61 | 34 | ||
U11 | RE | 0 | −9 | −12 | −10 | 20 | −10 | −16 | −30 | |
LE | 0 | −10 | −9 | −14 | 17 | −17 | 1 | −36 | ||
U12 | RE | 0 | 17 | 0 | 17 | 14 | 36 | 22 | 8 | |
LE | 0.5 | 14 | 3 | 34 | 25 | 16 | −30 | 13 | ||
U13 | RE | 0 | 20 | −2 | 38 | 31 | 24 | 26 | 20 | |
LE | 0 | −32 | 11 | 25 | 44 | 2 | 23 | 19 | ||
U14 | RE | 1.8 | −24 | −57 | −70 | 24 | 17 | 9 | −78 | |
LE | 0 | −31 | −52 | −9 | 15 | −24 | −36 | −70 | ||
U15 | RE | 0 | −5 | −2 | 18 | −28 | −13 | −22 | 9 | |
LE | 2.1 | −40 | −48 | −36 | −27 | −23 | −37 | −80 | ||
U16 | RE | 0.4 | −11 | −8 | −30 | −27 | −3 | −2 | −7 | |
LE | 0 | −3 | 4 | −27 | −3 | 7 | 11 | −24 |
ID | Eye | VA | P100 Latency (Deviation) | Visual Field Loss | Amblyopia | Mitochochondrial Mutation Heteroplasmy | Mt Haplogroup | Pedgiree | |||
---|---|---|---|---|---|---|---|---|---|---|---|
3460 G>A | 11778 G>A | 14484 T>C | |||||||||
LHON | C1 | RE | 1.8 | NR | 3 | - | 100 | H | 2 | ||
LE | 1.5 | NR | 3 | ||||||||
C2 | RE | 2.4 | NR | 3 | - | 100 | J | 3 | |||
LE | 2.1 | NR | 3 | ||||||||
C3 | RE | 0.9 | 137 (25) | 2 | - | 100 | J | 4 | |||
LE | 0.8 | 149 (37) | 2 | ||||||||
C4 | RE | 2.7 | NR | 4 | - | 100 | HV | 5 | |||
LE | 2.4 | NR | 4 | ||||||||
C5 | RE | 2.7 | 193 (81) | 4 | - | 100 | HV | 5 | |||
LE | 2.4 | NR | 4 | ||||||||
C6 | RE | 1 | NR | 3 | - | 80 | J | 6 | |||
LE | 1 | NR | 3 | ||||||||
C7 | RE | 1.8 | NR | 3 | - | 100 | HV | 7 | |||
LE | 1.8 | NR | 3 | ||||||||
E1 | RE | 1 | NR | 1 | + | 100 | U | 8 | |||
LE | 1 | NR | 1 | ||||||||
C8 | RE | 2.1 | NR | 4 | - | 100 | HV | 7 | |||
LE | 2.1 | NR | 4 | ||||||||
C9 | RE | 1.6 | NR | 3 | - | 100 | I | 10 | |||
LE | 1.9 | NR | 3 | ||||||||
C10 | RE | 1.4 | NR | 2 | - | HV | 11 | ||||
LE | 1.3 | NR | 2 | ||||||||
E2 | RE | 1.5 | NR | 3 | - | 100 | J | 13 | |||
LE | 1.5 | NR | 2 | ||||||||
Unaffected | U1 | RE | 0 | 118 (6) | 2 | + | 65 | U | 1 | ||
LE | 0.2 | 120 (8) | 2 | ||||||||
U2 | RE | 0 | 126 (14) | 2 | - | 98 | U | 1 | |||
LE | 0.2 | 130 (18) | 2 | ||||||||
U3 | RE | 0.1 | 112 (0) | 2 | - | 100 | H | 2 | |||
LE | 0.2 | 111 (−1) | 2 | ||||||||
U4 | RE | 0.1 | 107 (−5) | 2 | - | 100 | J | 3 | |||
LE | 0.2 | 107 (−5) | 1 | ||||||||
U5 | RE | 0 | NA | 2 | - | 100 | HV | 4 | |||
LE | 0 | NA | 1 | ||||||||
U6 | RE | 0.1 | 114 (2) | 1 | - | 100 | J | 5 | |||
LE | 0.1 | 117 (5) | 1 | ||||||||
U7 | RE | 0.1 | 110 (−2) | 1 | - | 88 | J | 6 | |||
LE | 0 | 108 (−4) | 1 | ||||||||
U8 | RE | 0.1 | 94 (−18) | 3 | + | 100 | HV | 7 | |||
LE | 2.4 | 121 (9) | 1 | ||||||||
U9 | RE | 0 | 107 (−5) | 1 | - | 100 | U | 8 | |||
LE | 0 | 114 (2) | 1 | ||||||||
U10 | RE | 0 | 102 (−10) | 1 | - | 100 | HV | 7 | |||
LE | 0 | 106 (−6) | 1 | ||||||||
U11 | RE | 0 | 100 (−12) | 1 | - | 100 | H | 9 | |||
LE | 0 | 106 (−6) | 1 | ||||||||
U12 | RE | 0 | 98 (−14) | 1 | - | 10 | I | 10 | |||
LE | 0.5 | 97 (−15) | 1 | ||||||||
U13 | RE | 0 | 103 (−9) | 1 | - | HV | 11 | ||||
LE | 0 | 106 (−6) | 11 | ||||||||
U14 | RE | 1.8 | 112 (0) | 3 | + | 100 | H | 12 | |||
LE | 0 | 120 (+8) | 2 | ||||||||
U15 | RE | 0 | 106 (−6) | 2 | + | 100 | H | 12 | |||
LE | 2.1 | 125 (13) | 3 | ||||||||
U16 | RE | 0.4 | 117 (5) | 2 | + | 100 | J | 13 | |||
LE | 0 | 111 (−1) | 2 |
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Quigley, C.; Stephenson, K.A.J.; Kenna, P.; Cassidy, L. Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups. Int. J. Mol. Sci. 2023, 24, 1068. https://doi.org/10.3390/ijms24021068
Quigley C, Stephenson KAJ, Kenna P, Cassidy L. Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups. International Journal of Molecular Sciences. 2023; 24(2):1068. https://doi.org/10.3390/ijms24021068
Chicago/Turabian StyleQuigley, Clare, Kirk A. J. Stephenson, Paul Kenna, and Lorraine Cassidy. 2023. "Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups" International Journal of Molecular Sciences 24, no. 2: 1068. https://doi.org/10.3390/ijms24021068