G4450A

# General Information

| **Position** | **4450** | **Variant** | **m.4450G\>A** | **Locus** | **MT\-TM** | **RNA** | **tRNA Met** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **mitoTIP** | 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.4450G\>A** variant in MT\-TM has been reported in 4 pedigrees. To date, 6 carriers have been reported. Reported mutation loads ranged from 0% to 77%, with a median of 36\.5% overall; affected carriers showed mutation loads from 0% to 77%, with a median of 41\.5%; unaffected carriers showed mutation loads from 0%, with a median of 0%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in urine (59%) and hair (41%) than in blood (20%). In one affected carrier, the mutation was undetectable in blood (0%), bone marrow (0%), and other tissue (0%) but exceeded 20% in muscle (67%). The main clinical manifestations among affected carriers included MELAS, splenic lymphoma, a lymphoid proliferation that fit the cytological, and histopathological criteria of a splenic lymphoma with villous lymphocytes, and muscle weakness in a limb girdle distribution, exercise intolerance, focal epilepsy, headache, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 4450 | m.4450G\>A | G4450A\-F1 | Japan | MELAS | ND | ND | 2019 | [30739820](https://pubmed.ncbi.nlm.nih.gov/30739820/) | Carrying A3242G |
| 2 | 4450 | m.4450G\>A | G4450A\-F1 | Japan | MELAS | ND | ND | 2019 | [30952460](https://pubmed.ncbi.nlm.nih.gov/30952460/) | Carrying A3242G |
| 3 | 4450 | m.4450G\>A | [G4450A\-F2](https://mitofam.com/doc/667/) | Denmark | MELAS | 1 | 0 | 2015 | [25468263](https://pubmed.ncbi.nlm.nih.gov/25468263/) |  |
| 4 | 4450 | m.4450G\>A | G4450A\-F3 | France | Splenic lymphoma with villous lymphocytes | ND | ND | 1998 | [9452079](https://pubmed.ncbi.nlm.nih.gov/9452079/) |  |
| 5 | 4450 | m.4450G\>A | G4450A\-F4 | France | Splenic lymphoma | ND | ND | 2001 | [11335700](https://pubmed.ncbi.nlm.nih.gov/11335700/) | Carrying T10410C, T10457C, C15913T |

# 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 | 4450 | m.4450G\>A | G4450A\-F1 | G4450A\-F1\-P1 | Uninf | F | Y | Y | A | 12 | 20% | / | 59% | 38% (Skin); 41% (H); 27% (Saliva); 35% (Nail) | MELAS; focal epilepsy, stroke\-like episodes, lactic acidosis, visual disturbance/headache, regression of intellectual ability | Carrying A3242G |
| 2 | 4450 | m.4450G\>A | G4450A\-F2 | G4450A\-F2\-I2 | Uninf | F | N | N | A | ND | 0 | 0 | 0 | / | Healthy | Carrying A3242G |
| 3 | 4450 | m.4450G\>A | G4450A\-F2 | G4450A\-F2\-II1 | De novo | F | Y | Y | A | 10 | 0 | 67% | / | 0%(BM);10%(F) | exercise intolerance, learning difficulty, and muscle weakness in a limb girdle distribution | Carrying A3242G |
| 4 | 4450 | m.4450G\>A | G4450A\-F3 | G4450A\-F3\-Ⅰ\-1 | Uninf | F | N | N | ND | ND | / | / | / | / | Healthy | Carrying A3242G |
| 5 | 4450 | m.4450G\>A | G4450A\-F3 | G4450A\-F3\-Ⅱ\-1 | Uninf | ND | Y | Y | ND | 72 | 75% | 44% | / | 77%(F);65%(blood polymorphonuclear cells);42%(blood platelets) | a lymphoid proliferation that fit the cytological, immunological, and histopathological criteria of a splenic lymphoma with villous lymphocytes; left costal margin discomfort and splenomegaly | Carrying A3242G |
| 6 | 4450 | m.4450G\>A | G4450A\-F4 | G4450A\-F4\-P1 | Uninf | M | Y | Y | ND | 60 | 75% | 44% | / | / | Splenic lymphoma | Carrying T10410C, T10457C, C15913T |

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