G10197A

# **General Information**

| **Position** | **10197** | **Variant** | **m.10197G\>A** | **Locus** | **MT\-ND3** | **Amino\-AcidChange** | **A47T** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **APOGEE2** | Likely\-pathogenic | **Pathogenicity** | Cfrm \[P] |

"Pathogenicity" status is derived from published literature or predictions from bioinformatics tools. Researchers and clinicians are cautioned that additional data and/or analysis may still be necessary to confirm the pathological significance of these variants. For more information, please see [Mitofam Info](https://mitofam.com/doc/385/).

# **Pedigree Information**

The **m.10197G\>A** variant in MT\-ND3 has been reported in 15 pedigrees. To date, 43 carriers have been reported. Homoplasmy was reported in 18/43 carriers (41\.9%), and 39/43 carriers (90\.7%) were affected. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in other tissue (30%) than in other tissue (10%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in urine (61%) than in blood (18\.6%). The main clinical manifestations among affected carriers included isolated optic neuropathy, LHON, hypotonia, ataxia, dysarthria, optic atrophy, leigh syndrome, athetosis, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 10197 | m.10197G\>A | [G10197A\-F1](https://mitofam.com/doc/1202/) | France | Leigh syndrome | 0 | 3 | 2007 | [17152068](https://pubmed.ncbi.nlm.nih.gov/17152068/) |  |
| 2 | 10197 | m.10197G\>A | [G10197A\-F2](https://mitofam.com/doc/1203/) | France | Leigh syndrome, dystonia | 1 | 0 | 2007 | [17152068](https://pubmed.ncbi.nlm.nih.gov/17152068/) |  |
| 3 | 10197 | m.10197G\>A |[ G10197A\-F3](https://mitofam.com/doc/1204/) | France | Leigh syndrome, dystonia | 1 | 2 | 2007 | [17152068](https://pubmed.ncbi.nlm.nih.gov/17152068/) |  |
| 4 | 10197 | m.10197G\>A | G10197A\-F4 | China | Leigh syndrome | ND | ND | 2018 | [30128709](https://pubmed.ncbi.nlm.nih.gov/30128709/) |  |
| 5 | 10197 | m.10197G\>A | G10197A\-F5 | China | Leigh syndrome | ND | ND | 2018 | [30128709](https://pubmed.ncbi.nlm.nih.gov/30128709/) |  |
| 6 | 10197 | m.10197G\>A | [G10197A\-F6](https://mitofam.com/doc/1205/) | China | Limited eye movement and ataxia Limited eye movement, ataxia, bulbar palsy | 0 | 1 | 2018 | [30128709](https://pubmed.ncbi.nlm.nih.gov/30128709/) |  |
| 7 | 10197 | m.10197G\>A | [G10197A\-F7](https://mitofam.com/doc/1206/) | United States | Dystonia | 0 | 1 | 2007 | [17413873](https://pubmed.ncbi.nlm.nih.gov/17413873/) |  |
| 8 | 10197 | m.10197G\>A | G10197A\-F8 | United States | Stroke\-like episodes | 0 | 0 | 2007 | [17413873](https://pubmed.ncbi.nlm.nih.gov/17413873/) |  |
| 9 | 10197 | m.10197G\>A | [G10197A\-F9 ](https://mitofam.com/doc/1207/)| China | LHON, optic neuropathy, dystonia | 2 | 15 | 2008 | [19458970](https://pubmed.ncbi.nlm.nih.gov/19458970/) |  |
| 10 | 10197 | m.10197G\>A | G10197A\-F10 | United States | LHON | 0 | 0 | 2018 | [30199507](https://pubmed.ncbi.nlm.nih.gov/30199507/) |  |
| 11 | 10197 | m.10197G\>A | G10197A\-F11 | United States | LHON | 0 | 0 | 2018 | [30899856](https://pubmed.ncbi.nlm.nih.gov/30899856/) |  |
| 12 | 10197 | m.10197G\>A | G10197A\-F12 | China | LHON, dystonia | ND | ND | 2015 | [32045392](https://pubmed.ncbi.nlm.nih.gov/32045392/) |  |
| 13 | 10197 | m.10197G\>A | [G10197A\-F13](https://mitofam.com/doc/1208/) | China | Leigh syndrome, dystonia | 0 | 1 | 2022 | [35907985](https://pubmed.ncbi.nlm.nih.gov/35907985/) |  |
| 14 | 10197 | m.10197G\>A | G10197A\-F14 | Portugal | Undetermined mitochondrial diseases | ND | ND | 2023 | [38465286](https://pubmed.ncbi.nlm.nih.gov/38465286/) |  |
| 15 | 10197 | m.10197G\>A | [G10197A\-F15](https://mitofam.com/doc/1209/) | China | Adult\-onset LS/LDYT overlap, gait abnormality, upper limb stiffness, visual disturbance, dysarthria, spasms, hypermyotonia/reflexia, cervical cord/brain lesions, poor visual acuity | 0 | 1 | 2025 | [39923090](https://pubmed.ncbi.nlm.nih.gov/39923090/) |  |

# **Carrier Information**

| **No.** | **Position** | **Variant** | **Family ID** | **Carrier ID** | **Type (Fam/De novo/Uninf)** | **Gender (F/M)** | **Proband (Y/N)** | **Affected (Y/N)** | **Die/Alive(D/A)** | **Age** | **Blood Mutant Level** | **Muscle Mutant level** | **Urine Mutant level** | **Other Mutant level** | **Clinical Features** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 10197 | m.10197G\>A | G10197A\-F1 | G10197A\-F1\-Ⅰ1 | Uninf | F | N | Y | A | 41 y | 67% | / | / | / | Hypotonia and mild mental retardation |  |
| 2 | 10197 | m.10197G\>A | G10197A\-F1 | G10197A\-F1\-Ⅱ1 | Fam | M | Y | Y | D | 5 mo | / | 100% | / | / | Leigh syndrome, growth retardation, hypotonia, psychomotor regression, seizures |  |
| 3 | 10197 | m.10197G\>A | G10197A\-F1 | G10197A\-F1\-Ⅱ2 | Fam | M | N | Y | D | 2 mo | 100% | / | / | 100%(Liver) | Anorexia, nystagmus, hypotonia |  |
| 4 | 10197 | m.10197G\>A | G10197A\-F1 | G10197A\-F1\-Ⅱ3 | Fam | F | N | Y | D | 8 mo | / | 100% | / | / | Hypotonia, growth retardation, liver enlargement, slight muscle atrophy, respiratory distress |  |
| 5 | 10197 | m.10197G\>A | G10197A\-F2 | G10197A\-F2\-Ⅰ1 | Uninf | F | N | N | A | 34 y | 50% | / | / | / | Healthy |  |
| 6 | 10197 | m.10197G\>A | G10197A\-F2 | G10197A\-F2\-Ⅱ1 | Fam | M | Y | Y | A | 5 y | / | 100% | / | 100%(F) | Leigh syndrome/dystonia, hypotonia, pyramidal syndrome, psychomotor retardation, strabismus, epilepsy, dystonia |  |
| 7 | 10197 | m.10197G\>A | G10197A\-F3 | G10197A\-F3\-Ⅰ1 | Uninf | F | N | Y | A | 37 y | 74% | 96% | / | / | Undetermined mitochondrial diseases |  |
| 8 | 10197 | m.10197G\>A | G10197A\-F3 | G10197A\-F3\-Ⅱ1 | Fam | F | N | N | A | 7 y | 73% | / | / | / | Healthy |  |
| 9 | 10197 | m.10197G\>A | G10197A\-F3 | G10197A\-F3\-Ⅱ2 | Fam | F | N | Y | A | 5 y | 100% | / | / | / | Seizures and developmental delay |  |
| 10 | 10197 | m.10197G\>A | G10197A\-F3 | G10197A\-F3\-Ⅱ3 | Fam | M | Y | Y | D | 11 mo | 100% | 100% | / | / | Leigh syndrome, motor delay/hypotonia, seizures |  |
| 11 | 10197 | m.10197G\>A | G10197A\-F4 | G10197A\-F4\-P1 | Uninf | F | Y | Y | ND | 2 y | 92% | / | / | / | Late\-onset Leigh syndrome, ataxia, bulbar palsy, developmental delay, failure to thrive |  |
| 12 | 10197 | m.10197G\>A | G10197A\-F5 | G10197A\-F5\-P1 | Uninf | M | Y | Y | ND | 6 y | 83% | / | / | / | Late\-onset Leigh syndrome, pyramidal signs, bulbar palsy, developmental delay, failure to thrive |  |
| 13 | 10197 | m.10197G\>A | G10197A\-F6 | G10197A\-F6\-Ⅰ1 | Uninf | F | Y | Y | ND | 14 y | 68% | / | / | / | Limited eye movement and ataxia |  |
| 14 | 10197 | m.10197G\>A | G10197A\-F6 | G10197A\-F6\-Ⅱ1 | Fam | M | Y | Y | ND | 22 y | 45% | / | / | / | Limited eye movement, ataxia, bulbar palsy |  |
| 15 | 10197 | m.10197G\>A | G10197A\-F7 | G10197A\-F7\-Ⅱ1 | Fam | F | Y | Y | A | 9 y | / | / | / | 98%(Other tissue) | Progressive generalized dystonia, gait ataxia, dysarthria |  |
| 16 | 10197 | m.10197G\>A | G10197A\-F7 | G10197A\-F7\-Ⅱ2 | Fam | M | N | Y | A | 4 y | / | / | / | 86%(Other tissue) | Progressive generalized dystonia, gait abnormality, dysarthria, ataxia |  |
| 17 | 10197 | m.10197G\>A | G10197A\-F8 | G10197A\-F8\-P1 | Uninf | M | Y | Y | A | Infancy | / | / | / | 80%(Other tissue) | Stroke\-like episodes |  |
| 18 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-II1 | Fam | F | N | Y | A | 75 y | Homo | / | / | / | Isolated optic neuropathy, sudden painless vision loss, right sensorineural deafness |  |
| 19 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-II2 | Fam | F | N | Y | A | ND | Homo | / | / | / | Isolated optic neuropathy |  |
| 20 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-III1 | Fam | M | N | N | A | ND | Homo | / | / | / | Healthy |  |
| 21 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-III2 | Fam | F | N | Y | A | ND | Homo | / | / | / | Isolated optic neuropathy |  |
| 22 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-III3 | Fam | M | N | Y | A | ND | Homo | / | / | / | Isolated optic neuropathy |  |
| 23 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-III4 | Fam | M | N | Y | A | ND | Homo | / | / | / | Isolated optic neuropathy |  |
| 24 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-III5 | Fam | M | N | Y | A | ND | Homo | / | / | / | Isolated optic neuropathy |  |
| 25 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-III6 | Fam | M | N | Y | A | ND | Homo | / | / | / | Isolated optic neuropathy |  |
| 26 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-III7 | Fam | F | N | Y | A | ND | Homo | / | / | / | Isolated optic neuropathy |  |
| 27 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-III8 | Fam | M | N | Y | A | ND | Homo | / | / | / | Spastic dystonia/LHON, gait/stiffness/athetosis, vision loss |  |
| 28 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-III9 | Fam | M | Y | Y | A | 39 y | Homo | / | / | / | Severe LDYT/LHON, vision loss, generalized spastic dystonia, optic atrophy |  |
| 29 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-III10 | Fam | F | N | Y | A | ND | Homo | / | / | / | Clumsiness, unstable gait, stiffness, optic atrophy |  |
| 30 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-IV1 | Fam | F | N | Y | A | ND | Homo | / | / | / | Isolated optic neuropathy |  |
| 31 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-IV2 | Fam | M | N | Y | A | 19 y | Homo | / | / | / | LHON, vision loss tremor, hyperreflexia, Hoffman signs, unstable tandem gait |  |
| 32 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-IV3 | Fam | F | N | N | A | ND | Homo | / | / | / | Healthy |  |
| 33 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-IV4 | Fam | F | N | Y | A | 22 y | Homo | / | / | / | Unstable gait, vision lossy, optic atrophy, macroglossia, athetosis/rigidity/hyperreflexia |  |
| 34 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-IV5 | Fam | F | N | Y | A | 20 y | Homo | / | / | / | Spastic dystonia, optic atrophy, spasticity, ankle clonus, athetosis, finger deformity, macroglossia, pes varus, forced crying |  |
| 35 | 10197 | m.10197G\>A | G10197A\-F9 | G10197A\-F9\-IV6 | Fam | M | N | Y | A | 18 y | Homo | / | / | / | Spastic gait |  |
| 36 | 10197 | m.10197G\>A | G10197A\-F10 | G10197A\-F10\-P1 | De novo | F | Y | Y | A | 48 y | / | / | / | 10\-30%(Other tissue) | LHON, subacute bilateral vision loss, central scotomas, visual improvement after idebenone |  |
| 37 | 10197 | m.10197G\>A | G10197A\-F11 | G10197A\-F11\-P1 | De novo | F | Y | Y | A | 48 y | / | / | / | \+ | LHON, bilateral vision loss |  |
| 38 | 10197 | m.10197G\>A | G10197A\-F12 | G10197A\-F12\-P1 | Uninf | M | Y | Y | A | 19 y | \+ | / | / | / | Sporadic isolated LHON, bilateral optic nerve increased T2 signal, severe visual acuity decline |  |
| 39 | 10197 | m.10197G\>A | G10197A\-F13 | G10197A\-F13\-Ⅰ1 | Uninf | F | N | Y | A | 22 y | 18\.6% | / | 61% | / | Adult\-onset Leigh syndrome, diplopia/slurred speech, gait disturbance/clumsiness, unable to live independently |  |
| 40 | 10197 | m.10197G\>A | G10197A\-F13 | G10197A\-F13\-Ⅱ1 | Fam | M | Y | Y | A | 14 y | 68% | / | 93% | / | Adult\-onset Leigh syndrome, diplopia, vision/hearing loss, ataxia, dysarthria, dysphagia, limb weakness, dystonia, cognitive impairment |  |
| 41 | 10197 | m.10197G\>A | G10197A\-F14 | G10197A\-F14\-P1 | Uninf | ND | Y | Y | ND | ND | / | / | / | / | Undetermined mitochondrial diseases |  |
| 42 | 10197 | m.10197G\>A | G10197A\-F15 | G10197A\-F15\-Ⅰ1 | Uninf | F | N | Y | A | ND | 16\.98% | / | / | / | Vision disturbance, epilepsy, abnormal gait by history |  |
| 43 | 10197 | m.10197G\>A | G10197A\-F15 | G10197A\-F15\-Ⅱ1 | Fam | M | Y | Y | A | Early 20s | 58\.12% | 77\.1% | / | / | Adult\-onset LS/LDYT overlap, gait abnormality, upper limb stiffness, visual disturbance, dysarthria, spasms, hypermyotonia, poor visual acuity |  |

For abbreviations and other usage instructions, please see [Mitofam Info](https://mitofam.com/doc/385/).