T9035C

# **General Information**

| **Position** | **9035** | **Variant** | **m.9035T\>C** | **Locus** | **MT\-ATP6** | **Amino\-AcidChange** | **L170P** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **APOGEE2** | Pathogenic | **Pathogenicity** | Cfrm \[LP] |

"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.9035T\>C** variant in MT\-ATP6 has been reported in 5 pedigrees. To date, 13 carriers have been reported. Homoplasmy was reported in 2/13 carriers (15\.4%), and 8/13 carriers (61\.5%) were affected. The main clinical manifestations among affected carriers included ataxia, complex HSP with asymmetric, late\-onset pure HSP, leg cramps after exercise, mental deficit, severe motor and speech delay, short stature and speech delay., sub\-acute ophthalmoplegia and ataxia with long tract signs, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 9035 | m.9035T\>C | [T9035C\-F2 ](https://mitofam.com/doc/1794/)| Belgium | severe motor/speech delay, spastic ataxia, epilepsy | 1 | 1 | 2022 | [35159298](https://pubmed.ncbi.nlm.nih.gov/35159298/) |  |
| 2 | 9035 | m.9035T\>C | T9035C\-F4 | Chile | Late\-onset hereditary spastic paraplegia | 2 | 1 | 2025 | [41222985](https://pubmed.ncbi.nlm.nih.gov/41222985/) |  |
| 3 | 9035 | m.9035T\>C | T9035C\-F5 | Belgium | ataxia, ophthalmoplegia, diplopia, visual loss, urinary retention, nystagmus | 0 | 0 | 2022 | [35159298](https://pubmed.ncbi.nlm.nih.gov/35159298/) |  |
| 4 | 9035 | m.9035T\>C | [T9035C\-F1](https://mitofam.com/doc/1793/) | UK | Adult\-onset spinocerebellar syndrome | 3 | 3 | 2012 | [22577227](https://pubmed.ncbi.nlm.nih.gov/22577227/) | Family B |
| 5 | 9035 | m.9035T\>C | T9035C\-F6 | France | Mental deficit; cerebellar syndrome; pyramidal syndrome; episodic paralysis; axonal sensory\-motor peripheral neuropathy. | 0 | 0 | 2020 | [32858252](https://pubmed.ncbi.nlm.nih.gov/32858252/) |  |

# **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 | 9035 | m.9035T\>C | T9035C\-F2 | T9035C\-F2\-II1 | Fam | M | Y | Y | A | 2 | Homo | / | / | Homo(F) | Severe motor and speech delay; spastic ataxia; hypotonia; brisk reflexes; extensor plantar responses |  |
| 2 | 9035 | m.9035T\>C | T9035C\-F2 | T9035C\-F2\-I2 | Uninf | F | N | N | A | ND | 31% | / | / | / | Healthy |  |
| 3 | 9035 | m.9035T\>C | T9035C\-F5 | T9035C\-F5\-P1 | Uninf | F | Y | Y | A | 19 | Homo | Homo | / | Homo(F) | Ataxia; ophthalmoplegia; ptosis; nystagmus; urinary retention; no cognitive impairment |  |
| 4 | 9035 | m.9035T\>C | T9035C\-F4 | T9035C\-F4\-P1 | Uninf | F | Y | Y | A | 67 | 83\.6% | / | / | / | Late\-onset pure HSP; lower extremity weakness and spasticity |  |
| 5 | 9035 | m.9035T\>C | T9035C\-F4 | T9035C\-F4\-P2 | Uninf | F | N | N | A | 46 | 90\.0% | / | / | / | Clinically unaffected carrier |  |
| 6 | 9035 | m.9035T\>C | T9035C\-F4 | T9035C\-F4\-P3 | Uninf | F | N | Y | A | 39 | 99\.7% | / | / | / | Complex HSP with asymmetric/multifocal sensorimotor axonal polyneuropathy |  |
| 7 | 9035 | m.9035T\>C | T9035C\-F1 | T9035C\-F1\-I2 | Fam | F | N | Y | A | 45 | 96% | / | / | / | Sub\-acute ophthalmoplegia and ataxia with long tract signs; residual midline ataxia; disordered eye movements; dysarthria. |  |
| 8 | 9035 | m.9035T\>C | T9035C\-F1 | T9035C\-F1\-I3 | Fam | F | N | Y | A | 43 | 90% | 96% | / | / | Leg cramps after exercise; gait ataxia; cerebellar dysarthria; pyramidal weakness; brisk reflexes. |  |
| 9 | 9035 | m.9035T\>C | T9035C\-F1 | T9035C\-F1\-II1 | Fam | F | N | Y | A | 4 | 95% | / | / | / | Short stature and speech delay. |  |
| 10 | 9035 | m.9035T\>C | T9035C\-F1 | T9035C\-F1\-II2 | Fam | F | N | N | A | ND | / | / | / | / | Healthy. |  |
| 11 | 9035 | m.9035T\>C | T9035C\-F1 | T9035C\-F1\-II3 | Fam | F | N | N | A | 11 | / | / | / | / | Healthy. |  |
| 12 | 9035 | m.9035T\>C | T9035C\-F1 | T9035C\-F1\-II4 | Fam | F | N | N | A | 8 | / | / | / | / | Healthy. |  |
| 13 | 9035 | m.9035T\>C | T9035C\-F6 | T9035C\-F6\-P1 | Uninf | ND | Y | Y | A | 31 | / | 100% | / | 100%(F) | Mental deficit; cerebellar syndrome; pyramidal syndrome; episodic paralysis; axonal sensory\-motor peripheral neuropathy. |  |

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