A3302G

# **General Information**

| **Position** | **3302** | **Variant** | **m.3302A\>G** | **Locus** | **MT\-TL1** | **RNA** | **tRNA Leu (UUR)** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **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.3302A\>G** variant in MT\-TL1 has been reported in 5 pedigrees. To date, 14 carriers have been reported. Reported mutation loads ranged from 23% to 96%, with a median of 61% overall; affected carriers showed mutation loads from 33% to 96%, with a median of 64\.5%; unaffected carriers showed mutation loads from 23% to 26%, with a median of 24\.5%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (76%) and breast issue (67%) than in blood (33%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (89\.5%) and fibroblasts (85\.8%) than in blood (36\.1%). The main clinical manifestations among affected carriers included respiratory failure, diabetes mellitus, muscle weakness, bilateral progressive ptosis, MELAS, pCOS\-Insulin resistance, short stature, slowly progressive myopathy, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 3302 | m.3302A\>G | [A3302G\-F1 ](https://mitofam.com/doc/2251/)| UK | Respiratory failure, muscle weakness | 0 | 3 | 1993 | [8366098](https://pubmed.ncbi.nlm.nih.gov/8366098/) |  |
| 2 | 3302 | m.3302A\>G | [A3302G\-F2](https://mitofam.com/doc/2252/) | The Netherlands | Cardiorespiratory failure | 1 | 1 | 2004 | [15351426](https://pubmed.ncbi.nlm.nih.gov/15351426/) |  |
| 3 | 3302 | m.3302A\>G |[ A3302G\-F3](https://mitofam.com/doc/2253/) | China | Insulin resistance in woman with PCOS | 2 | 2 | 2016 | [26335180](https://pubmed.ncbi.nlm.nih.gov/26335180/) |  |
| 4 | 3302 | m.3302A\>G | A3302G\-F4 | China | Short stature, muscle weakness, exercise intolerance, dyspnea, flu\-like illness, stair\-climbing difficulty, frequent falls, recurrent respiratory failure, respiratory muscle weakness. | ND | ND | 2017 | [28716227](https://pubmed.ncbi.nlm.nih.gov/28716227/) |  |
| 5 | 3302 | m.3302A\>G | A3302G\-F5 | Japan | MELAS | ND | ND | 2014 | [23582502](https://pubmed.ncbi.nlm.nih.gov/23582502/) |  |

# **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 | 3302 | m.3302A\>G | A3302G\-F1 | A3302G\-F1\-I2 | Uninf | F | N | Y | D | 35 | / | / | / | / | Respiratory failure |  |
| 2 | 3302 | m.3302A\>G | A3302G\-F1 | A3302G\-F1\-II1 | Fam | F | Y | Y | D | 22 | / | / | / | / | Respiratory failure, muscle weakness |  |
| 3 | 3302 | m.3302A\>G | A3302G\-F1 | A3302G\-F1\-II2 | Fam | F | N | Y | D | 11 | / | / | / | / | Respiratory failure |  |
| 4 | 3302 | m.3302A\>G | A3302G\-F1 | A3302G\-F1\-II3 | Fam | M | N | Y | D | 14 | / | / | / | / | Respiratory failure |  |
| 5 | 3302 | m.3302A\>G | A3302G\-F2 | A3302G\-F2\-I2 | Uninf | F | Y | Y | A | 40 | 33% | 76% | / | 52% (F), 58% (H), 67% (Breast issue) | Slowly progressive myopathy, shoulder girdle weakness, facial diplegia, external ophthalmoplegia, intestinal motility disturbances, chronic respiratory insufficiency, sensorineural deafness, first grade AV\-block, atrial tachycardia. |  |
| 6 | 3302 | m.3302A\>G | A3302G\-F2 | A3302G\-F2\-II1 | Fam | M | N | Y | D | 15 | 62% | 96% | / | 60% (F), 80% (H) | Bilateral progressive ptosis, proximal muscle weakness, complete external ophthalmoplegia, moderate facial diplegia, limb girdle\-type weakness, respiratory failure, severe lactic acidosis, ventricular fibrillation, asystole, anoxic brain injury, severe permanent brain damage. |  |
| 7 | 3302 | m.3302A\>G | A3302G\-F2 | A3302G\-F2\-II2 | Fam | F | N | N | A | ND | 26% | / | / | 23% (H) | Healthy |  |
| 8 | 3302 | m.3302A\>G | A3302G\-F3 | A3302G\-F3\-I2 | Uninf | F | N | Y | A | ND | / | / | / | / | Diabetes mellitus |  |
| 9 | 3302 | m.3302A\>G | A3302G\-F3 | A3302G\-F3\-II1 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 10 | 3302 | m.3302A\>G | A3302G\-F3 | A3302G\-F3\-II3 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 11 | 3302 | m.3302A\>G | A3302G\-F3 | A3302G\-F3\-II6 | Fam | F | N | Y | A | ND | / | / | / | / | Diabetes mellitus |  |
| 12 | 3302 | m.3302A\>G | A3302G\-F3 | A3302G\-F3\-III4 | Fam | F | Y | Y | A | 28 | / | / | / | / | PCOS\-Insulin resistance |  |
| 13 | 3302 | m.3302A\>G | A3302G\-F4 | A3302G\-F4\-P1 | Uninf | ND | Y | Y | D | 8 | / | / | / | / | Short stature, muscle weakness, exercise intolerance, dyspnea, flu\-like illness, stair\-climbing difficulty, frequent falls, recurrent respiratory failure, respiratory muscle weakness. |  |
| 14 | 3302 | m.3302A\>G | A3302G\-F5 | A3302G\-F5\-P1 | Uninf | M | Y | Y | A | 7 | 36\.1% | 89\.5% | / | 85\.8% (F) | MELAS |  |

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