T9176C

# **General Information**

| **Position** | **9176** | **Variant** | **m.9176T\>C** | **Locus** | **MT\-ATP6** | **Amino\-AcidChange** | **L217P** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **APOGEE2** | 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.9176T\>C** variant in MT\-ATP6 has been reported in 17 pedigrees. To date, 36 carriers have been reported. Homoplasmy was reported in 11/36 carriers (30\.6%), and 26/36 carriers (72\.2%) were affected. The main clinical manifestations among affected carriers included leigh syndrome, ataxia, axonal neuropathy, gait unsteadiness, pain, pyramidal signs, reduced vibration sense, adult\-onset Leigh syndrome, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 9176 | m.9176T\>C | T9176C\-F1 | Germany | Spinocerebellar ataxia | 0 | 1 | 2021 | [34037856](https://pubmed.ncbi.nlm.nih.gov/34037856/) |  |
| 2 | 9176 | m.9176T\>C | [T9176C\-F2](https://mitofam.com/doc/1804/) | Italy | Adult\-onset Leigh syndrome | 1 | 3 | 2011 | [21819970](https://pubmed.ncbi.nlm.nih.gov/21819970/) |  |
| 3 | 9176 | m.9176T\>C | [T9176C\-F3](https://mitofam.com/doc/1805/) | China | Mitochondrial ataxia | 0 | 1 | 2018 | [29756269](https://pubmed.ncbi.nlm.nih.gov/29756269/) |  |
| 4 | 9176 | m.9176T\>C | [T9176C\-F4](https://mitofam.com/doc/1806) | Spain | Leigh syndrome | 3 | 1 | 1997 | [9270604](https://pubmed.ncbi.nlm.nih.gov/9270604/) |  |
| 5 | 9176 | m.9176T\>C | [T9176C\-F5](https://mitofam.com/doc/1807) | Italy | Fulminant Leigh syndrome | 3 | 1 | 1998 | [9501263](https://pubmed.ncbi.nlm.nih.gov/9501263/) |  |
| 6 | 9176 | m.9176T\>C | T9176C\-F7 | Japan | Leigh syndrome/Leigh\-like syndrome | 0 | 0 | 2017 | [28429146](https://pubmed.ncbi.nlm.nih.gov/28429146/) |  |
| 7 | 9176 | m.9176T\>C | T9176C\-F8 | USA | Myeloneuropathy/CMT phenotype | 0 | 0 | 2019 | [31424416](https://pubmed.ncbi.nlm.nih.gov/31424416/) |  |
| 8 | 9176 | m.9176T\>C | T9176C\-F9 | Japan | Late\-onset Leigh syndrome | 0 | 0 | 2019 | [31625254](https://pubmed.ncbi.nlm.nih.gov/31625254/) |  |
| 9 | 9176 | m.9176T\>C | T9176C\-F10 | South Korea | Adult\-onset Leigh syndrome | 0 | 0 | 2017 | [29038134](https://pubmed.ncbi.nlm.nih.gov/29038134/) |  |
| 10 | 9176 | m.9176T\>C | T9176C\-F11 | Japan | Leigh syndrome | 0 | 0 | 2017 | [28429146](https://pubmed.ncbi.nlm.nih.gov/28429146/) |  |
| 11 | 9176 | m.9176T\>C | [T9176C\-F14](https://mitofam.com/doc/1808) | France | HSP\-like disorder | 0 | 5 | 2011 | [20656066](https://pubmed.ncbi.nlm.nih.gov/20656066/) |  |
| 12 | 9176 | m.9176T\>C | [T9176C\-F15](https://mitofam.com/doc/1809) | Germany | Charcot\-Marie\-Tooth hereditary neuropathy | 0 | 2 | 2012 | [22971232](https://pubmed.ncbi.nlm.nih.gov/22971232/) |  |
| 13 | 9176 | m.9176T\>C | [T9176C\-F16](https://mitofam.com/doc/1810) | USA | Familial bilateral striatal necrosis; Leigh\-like syndrome | 3 | 1 | 1995 | [7668837](https://pubmed.ncbi.nlm.nih.gov/7668837/) |  |
| 14 | 9176 | m.9176T\>C | T9176C\-F17 | France | Episodic paralysis; axonal sensory\-motor peripheral neuropathy. | 0 | 0 | 2020 | [32858252](https://pubmed.ncbi.nlm.nih.gov/32858252/) |  |
| 15 | 9176 | m.9176T\>C | T9176C\-F20 | China | Leigh syndrome | ND | ND | 2020 | [32348839](https://pubmed.ncbi.nlm.nih.gov/32348839/) |  |
| 16 | 9176 | m.9176T\>C | T9176C\-F21 | China | Leigh syndrome | ND | ND | 2020 | [32348839](https://pubmed.ncbi.nlm.nih.gov/32348839/) |  |
| 17 | 9176 | m.9176T\>C | T9176C\-F22 | China | Late\-onset Leigh syndrome | 0 | 0 | 2018 | [30128709](https://pubmed.ncbi.nlm.nih.gov/30128709/) |  |

# **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 | 9176 | m.9176T\>C | T9176C\-F1 | T9176C\-F1\-I1 | Uninf | F | Y | Y | A | 75 | 99% | / | / | / | spinocerebellar ataxia; dysarthria; cerebellar atrophy |  |
| 2 | 9176 | m.9176T\>C | T9176C\-F2 | T9176C\-F2\-III2 | Fam | F | Y | Y | A | 26 | \>99% | \>99% | \>99% | \>99%(BM); \>99%(F); \>99%(Myoblast) | Adult\-onset Leigh syndrome; ptosis; gaze paresis; ataxia; seizures |  |
| 3 | 9176 | m.9176T\>C | T9176C\-F2 | T9176C\-F2\-II2 | Fam | F | N | ND | A | ND | 30\.5% | / | / | / | Mild mental retardation |  |
| 4 | 9176 | m.9176T\>C | T9176C\-F3 | T9176C\-F3\-II1 | Fam | M | Y | Y | A | 35 | Homo | / | / | / | Cerebellar ataxia; nystagmus; muscle weakness; tendon areflexia; Babinski sign |  |
| 5 | 9176 | m.9176T\>C | T9176C\-F3 | T9176C\-F3\-I2 | Uninf | F | N | Y | A | ND | / | / | / | / | Gait imbalance/cerebellar ataxia |  |
| 6 | 9176 | m.9176T\>C | T9176C\-F4 | T9176C\-F4\-III1 | Fam | M | Y | Y | D | 4 | / | \>99% | / | / | Leigh syndrome; died shortly after admission |  |
| 7 | 9176 | m.9176T\>C | T9176C\-F4 | T9176C\-F4\-II2 | Fam | F | N | Y | A | 22 | 93% | / | / | / | Developmental delay; progressive mental retardation; gait unsteadiness; nystagmus; pyramidal signs; ataxia |  |
| 8 | 9176 | m.9176T\>C | T9176C\-F4 | T9176C\-F4\-II1 | Fam | M | N | N | A | ND | 88% | / | / | / | Healthy |  |
| 9 | 9176 | m.9176T\>C | T9176C\-F4 | T9176C\-F4\-I2 | Fam | F | N | N | A | ND | 76% | / | / | / | Healthy |  |
| 10 | 9176 | m.9176T\>C | T9176C\-F4 | T9176C\-F4\-I3 | Fam | F | N | N | A | ND | 15% | / | / | / | Healthy |  |
| 11 | 9176 | m.9176T\>C | T9176C\-F5 | T9176C\-F5\-III1 | Fam | M | Y | Y | D | 9mo | / | \>95% | / | \>95%(F) | Fulminant Leigh syndrome; coma; periodic breathing; seizures; pyramidal signs; died |  |
| 12 | 9176 | m.9176T\>C | T9176C\-F5 | T9176C\-F5\-II2 | Fam | F | N | N | A | ND | 50% | / | / | / | Healthy |  |
| 13 | 9176 | m.9176T\>C | T9176C\-F5 | T9176C\-F5\-II3 | Fam | M | N | N | A | ND | 70% | / | / | / | Healthy |  |
| 14 | 9176 | m.9176T\>C | T9176C\-F5 | T9176C\-F5\-I2 | Uninf | F | N | N | A | ND | 10% | / | / | / | Healthy |  |
| 15 | 9176 | m.9176T\>C | T9176C\-F7 | T9176C\-F7\-P1 | Fam | ND | Y | Y | A | ND | 100% | / | / | / | Leigh syndrome |  |
| 16 | 9176 | m.9176T\>C | T9176C\-F11 | T9176C\-F11\-P1 | Fam | ND | Y | Y | A | ND | 100% | / | / | / | Leigh syndrome |  |
| 17 | 9176 | m.9176T\>C | T9176C\-F8 | T9176C\-F8\-P1 | Fam | M | Y | Y | A | 53 | Homo | / | / | / | Myeloneuropathy; high arches; hammertoes; progressive lower extremity weakness and stiffness; sensory signs |  |
| 18 | 9176 | m.9176T\>C | T9176C\-F9 | T9176C\-F9\-P1 | Uninf | M | Y | Y | A | 10 | Homo | / | / | / | Late\-onset Leigh syndrome; bilateral ptosis and external ophthalmoplegia |  |
| 19 | 9176 | m.9176T\>C | T9176C\-F10 | T9176C\-F10\-P1 | Uninf | M | Y | Y | A | 20 | Homo | / | / | / | Adult\-onset Leigh syndrome; bilateral fatigable ptosis; periaqueductal gray MRI lesions; elevated CSF lactate |  |
| 20 | 9176 | m.9176T\>C | T9176C\-F14 | T9176C\-F14\-III3 | Fam | F | N | Y | A | 59 | Homo | Homo | Homo | F Homo | Painful legs; mild sensory loss; axonal neuropathy; disability grade 2\. |  |
| 21 | 9176 | m.9176T\>C | T9176C\-F14 | T9176C\-F14\-III5 | Fam | M | N | Y | A | 56 | Homo | Homo | Homo | F Homo | Severe HSP\-like disorder; wheelchair\-bound; spasticity; weakness; pain; axonal neuropathy; diabetes; cardiomyopathy; arrhythmia; cerebellar syndrome. |  |
| 22 | 9176 | m.9176T\>C | T9176C\-F14 | T9176C\-F14\-III7 | Fam | F | N | Y | A | 49 | Homo | Homo | Homo | F Homo | Gait impairment; stiffness; painful legs; pyramidal syndrome; reduced vibration sense; disability grade 3\. |  |
| 23 | 9176 | m.9176T\>C | T9176C\-F14 | T9176C\-F14\-III8 | Fam | M | Y | Y | A | 48 | Homo | Homo | Homo | F Homo | Proband; wheelchair\-bound spastic paraplegia; hyperreflexia; pain; axonal neuropathy; disability grade 4\. |  |
| 24 | 9176 | m.9176T\>C | T9176C\-F14 | T9176C\-F14\-III9 | Fam | F | N | Y | A | 38 | Homo | Homo | Homo | F Homo | Lower\-limb spasticity after exercise; pain; reduced vibration sense; disability grade 1\. |  |
| 25 | 9176 | m.9176T\>C | T9176C\-F15 | T9176C\-F15\-II5 | Fam | F | N | Y | A | 73 | \+ | / | / | / | Mild high\-arched feet; reduced vibration sense; absent Achilles reflexes; severe chronic motor and sensory axonal neuropathy; arrhythmia; cataract; diabetes. |  |
| 26 | 9176 | m.9176T\>C | T9176C\-F15 | T9176C\-F15\-III1 | Fam | F | Y | Y | A | 49 | Homo | Homo | / | / | Index patient; CMT2\-like axonal neuropathy; pes cavus; gait unsteadiness; distal weakness/atrophy; paraesthesia; mild cerebellar atrophy. |  |
| 27 | 9176 | m.9176T\>C | T9176C\-F15 | T9176C\-F15\-IV1 | Fam | F | N | Y | A | 24 | Homo | / | / | / | Similar axonal CMT phenotype; pes cavus; claw toes; gait unsteadiness; reduced vibration sense. |  |
| 28 | 9176 | m.9176T\>C | T9176C\-F16 | T9176C\-F16\-II1 | Fam | M | Y | Y | A | 6 | \>99% | \>99% | / | \>99%(F) | Bilateral striatal necrosis; Leigh\-like syndrome; developmental delay; dystonia; external ophthalmoparesis; basal ganglia MRI lesions. |  |
| 29 | 9176 | m.9176T\>C | T9176C\-F16 | T9176C\-F16\-II2 | Fam | M | N | Y | A | 11 | 98% | / | / | / | Bilateral striatal necrosis; learning disability; speech/language regression; motor incoordination; basal ganglia MRI lesions. |  |
| 30 | 9176 | m.9176T\>C | T9176C\-F16 | T9176C\-F16\-I2 | Uninf | F | N | N | A | ND | 7% | / | / | / | Healthy. |  |
| 31 | 9176 | m.9176T\>C | T9176C\-F16 | T9176C\-F16\-II3 | Fam | M | N | N | A | 13 | 55% | / | / | / | Healthy. |  |
| 32 | 9176 | m.9176T\>C | T9176C\-F16 | T9176C\-F16\-II4 | Fam | F | N | N | A | 7 | 76% | / | / | / | Healthy. |  |
| 33 | 9176 | m.9176T\>C | T9176C\-F17 | T9176C\-F17\-P1 | Uninf | ND | Y | Y | A | 36 | 100% | / | / | / | Episodic paralysis; axonal sensory\-motor peripheral neuropathy. |  |
| 34 | 9176 | m.9176T\>C | T9176C\-F20 | T9176C\-F20\-P1 | Uninf | M | Y | Y | A | 1 | 99\.6% | / | / | / | Leigh syndrome; progressive follow\-up; lactate 2\.7 mmol/L. |  |
| 35 | 9176 | m.9176T\>C | T9176C\-F21 | T9176C\-F21\-P1 | Uninf | F | Y | Y | A | 12 | 99\.5% | / | / | / | Leigh syndrome; myopathic and neuropathic EMG; ST EKG; lactate 5\.5 mmol/L; progressive follow\-up. |  |
| 36 | 9176 | m.9176T\>C | T9176C\-F22 | T9176C\-F22\-P1 | Uninf | M | Y | Y | ND | 27 onset | 99% | / | / | / | Late\-onset Leigh syndrome; mental retardation; limited extraocular movements; ataxia; pyramidal signs; bulbar palsy. |  |

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