G4296A

# **General Information**

| **Position** | **4296** | **Variant** | **m.4296G\>A** | **Locus** | **MT\-TI** | **RNA** | **tRNA Ile** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **mitoTIP** | 46\.60% | **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.4296G\>A** variant in MT\-TI has been reported in 4 pedigrees. To date, 12 carriers have been reported. Reported mutation loads ranged from 4% to 97\.9%, with a median of 27\.8% overall; affected carriers showed mutation loads from 78% to 97\.9%, with a median of 88\.5%; unaffected carriers showed mutation loads from 4% to 58%, with a median of 4%. The main clinical manifestations among affected carriers included developmental delay, leigh syndrome, leigh\-like syndrome, bradykinesia, clumsiness, dysarthria, encephalopathy, hypogonadism, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 4296 | m.4296G\>A | [G4296A\-F1](https://mitofam.com/doc/626/) | Spain | Leigh syndrome | 2 | 0 | 2012 | [21982779](https://pubmed.ncbi.nlm.nih.gov/21982779/) |  |
| 2 | 4296 | m.4296G\>A | [G4296A\-F2](https://mitofam.com/doc/628/) | USA | Developmental delay, hypotonia, encephalopathy, peripheral neuropathy | 2 | 0 | 2013 | [23288206](https://pubmed.ncbi.nlm.nih.gov/23288206/) |  |
| 3 | 4296 | m.4296G\>A | [G4296A\-F3 ](https://mitofam.com/doc/629/)| Finland | Juvenile parkinsonism, hypogonadism and Leigh\-like MRI changes | 2 | 0 | 2013 | [23395828](https://pubmed.ncbi.nlm.nih.gov/23395828/) |  |
| 4 | 4296 | m.4296G\>A | [G4296A\-F4](https://mitofam.com/doc/630/) | China | Leigh Syndrome | 2 | 0 | 2019 | <https://d.wanfangdata.com.cn/periodical/zgsyzdx201905039> | Carrying NUBPL c.C169G |

# **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 | 4296 | m.4296G\>A | G4296A\-F1 | G4296A\-F1\-I2 | Uninf | F | N | N | A | ND | 4% | / | 4% | 4%(BM) | Healthy |  |
| 2 | 4296 | m.4296G\>A | G4296A\-F1 | G4296A\-F1\-II1 | Fam | F | N | N | A | ND | 4% | / | 4% | 4%(BM) | Healthy |  |
| 3 | 4296 | m.4296G\>A | G4296A\-F1 | G4296A\-F1\-II2 | Fam | F | Y | Y | A | 6 | 78% | / | / | 85%(F) | Leigh syndrome |  |
| 4 | 4296 | m.4296G\>A | G4296A\-F2 | G4296A\-F2\-I2 | Uninf | F | N | N | A | 30 | 27\.8% | / | / | / | Healthy |  |
| 5 | 4296 | m.4296G\>A | G4296A\-F2 | G4296A\-F2\-II1 | Fam | F | N | N | A | 15 | 31\.6% | / | / | / | Healthy |  |
| 6 | 4296 | m.4296G\>A | G4296A\-F2 | G4296A\-F2\-II2 | Fam | F | Y | Y | A | 4 | 97\.9% | / | / | / | Developmental delay, hypotonia, encephalopathy, peripheral neuropathy |  |
| 7 | 4296 | m.4296G\>A | G4296A\-F3 | G4296A\-F3\-I2 | Uninf | F | N | N | A | ND | 58% | / | / | / | Healthy |  |
| 8 | 4296 | m.4296G\>A | G4296A\-F3 | G4296A\-F3\-II1 | Fam | M | Y | Y | A | 17 | 95% | / | / | / | Leigh\-like syndrome, parkinsonism, hypogonadism, psychomotor retardation, dysarthria, clumsiness, limb rigidity, bradykinesia, developmental delay |  |
| 9 | 4296 | m.4296G\>A | G4296A\-F3 | G4296A\-F3\-II2 | Fam | F | N | N | A | 14 | / | / | / | / | Healthy |  |
| 10 | 4296 | m.4296G\>A | G4296A\-F4 | G4296A\-F4\-I2 | Uninf | F | N | N | A | ND | 6\.77% | / | / | / | Healthy |  |
| 11 | 4296 | m.4296G\>A | G4296A\-F4 | G4296A\-F4\-II1 | Fam | F | N | N | A | 10 | / | / | / | / | Healthy |  |
| 12 | 4296 | m.4296G\>A | G4296A\-F4 | G4296A\-F4\-II2 | Fam | F | Y | Y | A | 4 | / | / | / | 88\.5%(Cerebrospinal fluid) | Leigh Syndrome | Carrying NUBPL c.C169G |

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