T9478C

# **General Information**

| **Position** | **9478** | **Variant** | **m.9478T\>C** | **Locus** | **MT\-CO3** | **Amino\-AcidChange** | **V91A** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **APOGEE2** | Likely\-benign | **Pathogenicity** | Reported \[VUS] |

"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.9478T\>C** variant in MT\-CO3 has been reported in 2 pedigrees. To date, 6 carriers have been reported. Reported mutation loads ranged from 0% to 95%, with a median of 86% overall; affected carriers showed mutation loads from 0% to 95%, with a median of 88\.5%; unaffected carriers showed mutation loads from 0% to 87%, with a median of 73\.5%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in blood (89%) and bone marrow (95%) than in hair (4%). In one affected carrier, the mutation was undetectable in hair (0%) but exceeded 20% in blood (88%) and bone marrow (91%). Similar tissue\-specific differences were observed in 1 additional carriers. The main clinical manifestations among affected carriers included leigh syndrome, bilateral putamen MRI hyperintensities, distal amyotrophia, elevated lactate reported groupwise, neurologic abnormalities, nystagmus, pes cavus, spastic paraplegia, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 9478 | m.9478T\>C | [T9478C\-F1](https://mitofam.com/doc/1680/) | Tunisia | Leigh syndrome | 6 | 1 | 2011 | [20525945](https://pubmed.ncbi.nlm.nih.gov/20525945/) |  |
| 2 | 9478 | m.9478T\>C |[ T9478C\-F2](https://mitofam.com/doc/1681/) | Tunisia | Leigh syndrome | 0 | 1 | 2012 | [23301511](https://pubmed.ncbi.nlm.nih.gov/23301511/) |  |

# **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 | 9478 | m.9478T\>C | T9478C\-F1 | T9478C\-F1\-IV1 | Fam | M | Y | Y | A | 43 | 89% | / | / | 95%(BM); 4%(H) | Leigh syndrome; childhood visual loss/nystagmus, dystonic choreoathetosis, spastic paraplegia, vertical ophthalmoplegia, distal amyotrophia, pes cavus |  |
| 2 | 9478 | m.9478T\>C | T9478C\-F1 | T9478C\-F1\-IV2 | Fam | F | N | Y | A | 26 | 88% | / | / | 91%(BM); 0%(H) | Leigh syndrome; visual loss/nystagmus, mental retardation, choreic movements, head tremor, spastic paraplegia, distal amyotrophia, pes cavus |  |
| 3 | 9478 | m.9478T\>C | T9478C\-F1 | T9478C\-F1\-III1 | Fam | F | N | N | A | ND | 85% | / | / | 87%(BM); 0%(H) | Healthy/asymptomatic mother |  |
| 4 | 9478 | m.9478T\>C | T9478C\-F1 | T9478C\-F1\-IV3 | Fam | M | N | N | A | ND | 62% | / | / | BM ND; H ND | Healthy/asymptomatic brother |  |
| 5 | 9478 | m.9478T\>C | T9478C\-F2 | T9478C\-F2\-I1 | Uninf | ND | ND | Y | ND | ND | \+ | / | / | / | Leigh syndrome; elevated lactate reported groupwise; bilateral putamen MRI hyperintensities; neurologic abnormalities |  |
| 6 | 9478 | m.9478T\>C | T9478C\-F2 | T9478C\-F2\-II1 | Fam | ND | ND | Y | ND | ND | \+ | / | / | / | Leigh syndrome; elevated lactate reported groupwise; bilateral putamen MRI hyperintensities; neurologic abnormalities |  |

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