G4284A

# **General Information**

| **Position** | **4284** | **Variant** | **m.4284G\>A** | **Locus** | **MT\-TI** | **RNA** | **tRNA Ile** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **mitoTIP** | 35\.30% | **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.4284G\>A** variant in MT\-TI has been reported in 2 pedigrees. To date, 6 carriers have been reported. Reported mutation loads ranged from 0% to 100%, with a median of 30% overall; affected carriers showed mutation loads from 20% to 100%, with a median of 45%; unaffected carriers showed mutation loads from 0% to 20%, with a median of 0%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (55%), urine (40%), and hair (50%) than in blood (20%) and bone marrow (20%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (80%) than in urine (20%). The main clinical manifestations among affected carriers included myoclonus, epilepsy, dysarthria, truncal ataxia, spastic paraparesis, ataxia, clumsy walk, cognitive decline, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 4284 | m.4284G\>A | [G4284A\-F1](https://mitofam.com/doc/623/) | Italy | Spastic paraparesis, myoclonus, ataxia, dysarthria, ophthalmoparesis, hearing loss, cognitive impairment, epilepsy, diabetes, lipoma, hypogonadism, cardiomyopathy, heart failure | 2 | 6 | 2002 | [11782991](https://pubmed.ncbi.nlm.nih.gov/11782991/) |  |
| 2 | 4284 | m.4284G\>A | [G4284A\-F2](https://mitofam.com/doc/624/) | Germany | Myoclonus, epilepsy, ataxia, cognitive decline, learning disability | 7 | 0 | 2011 | [21766266](https://pubmed.ncbi.nlm.nih.gov/21766266/) |  |

# **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 | 4284 | m.4284G\>A | G4284A\-F1 | G4284A\-F1\-III2 | Fam | M | Y | Y | A | 35 | 20% | 55% | 40% | 50%(H),30%(F),20%(BM) | Spastic paraparesis, genu valgum, clumsy walk, poroencephalic cavitation, corpus callosum atrophy |  |
| 2 | 4284 | m.4284G\>A | G4284A\-F1 | G4284A\-F1\-III1 | Fam | M | N | Y | D | 27 | / | 90% | / | / | Epilepsy, myoclonus, truncal ataxia, dysarthria, dysmetria, deafness, mental deterioration, macular degeneration, hemiparesis, diabetes, lipoma, hypogonadism, dilated cardiomyopathy, heart failure |  |
| 3 | 4284 | m.4284G\>A | G4284A\-F1 | G4284A\-F1\-II2 | Fam | F | N | Y | A | 64 | 30% | 80% | 20% | / | Truncal ataxia, dysarthria, myoclonus, proximal weakness, ophthalmoparesis, hearing loss, mental regression, diabetes mellitus |  |
| 4 | 4284 | m.4284G\>A | G4284A\-F1 | G4284A\-F1\-III3 | Fam | M | N | N | A | 33 | 0 | / | 0 | / | Healthy |  |
| 5 | 4284 | m.4284G\>A | G4284A\-F2 | G4284A\-F2\-I2 | Uninf | F | N | N | A | ND | 20% | / | / | / | Healthy |  |
| 6 | 4284 | m.4284G\>A | G4284A\-F2 | G4284A\-F2\-II1 | Fam | F | Y | Y | A | 12 | 80% | 1 | / | / | Myoclonus, epilepsy, ataxia, cognitive decline, learning disability |  |

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