A3243T

# **General Information**

| **Position** | **3243** | **Variant** | **m.3243A\>T** | **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.3243A\>T** variant in MT\-TL1 has been reported in 7 pedigrees. To date, 10 carriers have been reported. Homoplasmy was reported in 1/10 carriers (10%), and 8/10 carriers (80%) were affected. In one unaffected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in urine (24%) and bone marrow (54%) than in blood (12%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in blood (46%), muscle (87%), and urine (88%) than in bone marrow (16%). Similar tissue\-specific differences were observed in 4 additional carriers. The main clinical manifestations among affected carriers included encephalomyopathy, MELAS, cataracts, muscle weakness, short stature, visual impairment, exercise\-induced myalgia, hearing loss, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 3243 | m.3243A\>T | [A3243T\-F1](https://mitofam.com/doc/2227/) | UK | Progressive sensorineural hearing loss, recurrent keratitis, visual impairment, short stature, basal ganglia and corneal calcification, cataracts, epilepsy. | ND | ND | 2010 | [20471262](https://pubmed.ncbi.nlm.nih.gov/20471262/) |  |
| 2 | 3243 | m.3243A\>T | [A3243T\-F2 ](https://mitofam.com/doc/2228/)| UK | MELAS | 1 | 1 | 2025 | [40787093](https://pubmed.ncbi.nlm.nih.gov/40787093/) |  |
| 3 | 3243 | m.3243A\>T | A3243T\-F3 | Israel | Encephalomyopathy | ND | ND | 1997 | [9168904](https://pubmed.ncbi.nlm.nih.gov/9168904/) |  |
| 4 | 3243 | m.3243A\>T | A3243T\-F4 | USA | Progressive cerebral vascular degeneration, encephalomyopathy | ND | ND | 2008 | [18203188](https://pubmed.ncbi.nlm.nih.gov/18203188/) |  |
| 5 | 3243 | m.3243A\>T | A3243T\-F5 | UK | Left\-sided ptosis, mild axial muscle weakness, difficulty maintaining bent\-knee posture, progressive weakness, severe exercise intolerance, proximal hip weakness, worsening bilateral ptosis, complete ophthalmoplegia, bilateral visual impairment. | ND | ND | 2010 | [20471262](https://pubmed.ncbi.nlm.nih.gov/20471262/) |  |
| 6 | 3243 | m.3243A\>T | A3243T\-F6 | Switzerland | Exercise\-induced myalgia and rhabdomyolysis | ND | ND | 2012 | [23220830](https://pubmed.ncbi.nlm.nih.gov/23220830/) |  |
| 7 | 3243 | m.3243A\>T | A3243T\-F7 | Japan | MELAS | ND | ND | 2018 | [30210801](https://pubmed.ncbi.nlm.nih.gov/30210801/) |  |

# **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 | 3243 | m.3243A\>T | A3243T\-F1 | A3243T\-F1\-I2 | Uninf | F | N | N | A | ND | 12% | / | 24% | 54% (BM) | Healthy |  |
| 2 | 3243 | m.3243A\>T | A3243T\-F1 | A3243T\-F1\-II1 | Fam | M | Y | Y | A | 22 | 46% | 87% | 88% | 16% (BM) | Progressive sensorineural hearing loss, recurrent keratitis, visual impairment, short stature, basal ganglia and corneal calcification, cataracts, epilepsy. |  |
| 3 | 3243 | m.3243A\>T | A3243T\-F2 | A3243T\-F2\-I2 | Uninf | F | N | Y | A | ND | 6% | 26% | / | 14% (BM) | Hearing loss, cataracts, nyctalopia, pigmentary retinopathy, macular atrophy, rod\-cone dystrophy, macular dysfunction, exercise intolerance, progressive muscle weakness. |  |
| 4 | 3243 | m.3243A\>T | A3243T\-F2 | A3243T\-F2\-II1 | Fam | M | Y | Y | D | 9 | 45% | 82% | / | 61% (F), 83% (Renal tissue) | MELAS |  |
| 5 | 3243 | m.3243A\>T | A3243T\-F2 | A3243T\-F2\-II2 | Fam | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 6 | 3243 | m.3243A\>T | A3243T\-F3 | A3243T\-F3\-P1 | Uninf | F | Y | Y | A | 6 | 13\.8% | 81\.4% | / | 69\.3% (F) | Encephalomyopathy, muscle weakness, fatigue |  |
| 7 | 3243 | m.3243A\>T | A3243T\-F4 | A3243T\-F4\-P1 | Uninf | F | Y | Y | D | 7 | 50% | Homo | / | 50% (F) | Progressive cerebral vascular degeneration, encephalomyopathy |  |
| 8 | 3243 | m.3243A\>T | A3243T\-F5 | A3243T\-F5\-P1 | Uninf | F | Y | Y | A | 11 | 5\~10% | 60% | / | / | Left\-sided ptosis, mild axial muscle weakness, difficulty maintaining bent\-knee posture, progressive weakness, severe exercise intolerance, proximal hip weakness, worsening bilateral ptosis, complete ophthalmoplegia, bilateral visual impairment. |  |
| 9 | 3243 | m.3243A\>T | A3243T\-F6 | A3243T\-F6\-P1 | Uninf | M | Y | Y | A | 32 | / | 30% | / | / | Exercise\-induced myalgia, rhabdomyolysis |  |
| 10 | 3243 | m.3243A\>T | A3243T\-F7 | A3243T\-F7\-P1 | Uninf | M | Y | Y | A | 11 | 22% | / | / | 35% (F), 26% (H) | MELAS, visual impairment, muscle weakness, short stature |  |

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