A3252G

# **General Information**

| **Position** | **3252** | **Variant** | **m.3252A\>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.3252A\>G** variant in MT\-TL1 has been reported in 3 pedigrees. To date, 9 carriers have been reported. Reported mutation loads ranged from 3% to 78%, with a median of 30% overall; affected carriers showed mutation loads from 5% to 78%, with a median of 45%; unaffected carriers showed mutation loads from 3% to 7%, with a median of 6%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in urine (10%) than in bone marrow (5%). In one unaffected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (7%) and fibroblasts (6%) than in blood (less than 3%). Similar tissue\-specific differences were observed in 1 additional carriers. The main clinical manifestations among affected carriers included migraine, hearing loss, encephalomyopathy, MELAS, mELAS overlapping syndrome, MERRF, progressive generalised weakness, cognitive delay, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 3252 | m.3252A\>G | [A3252G\-F1](https://mitofam.com/doc/2232/) | Spain | Migraine, recurrent stroke\-like episodes, photoparoxistic response, epilepsy, exercise intolerance, myopathy, gastro\-intestinal symptoms, hearing loss, decreased vision, cognitive delay, MELAS | 1 | 1 | 2015 | [25765153](https://pubmed.ncbi.nlm.nih.gov/25765153/) |  |
| 2 | 3252 | m.3252A\>G | [A3252G\-F2](https://mitofam.com/doc/2233/) | UK | Encephalomyopathy | 2 | 2 | 1993 | [8111377](https://pubmed.ncbi.nlm.nih.gov/8111377/) |  |
| 3 | 3252 | m.3252A\>G | A3252G\-F3 | China | MERRF/MELAS overlapping syndrome | 0 | 0 | 2023 | Tan YY, Tee TY, Chew FY, Kok HT, Abd Rani NH, Ngu LH, Viswanathan S. Mitochondrial DNA 3252A\> G mutation presenting as MERRF/MELAS overlapping syndrome: A case report. Neurology Asia. 2023 Dec 30;28(4\):1073\-6\. |  |

# **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 | 3252 | m.3252A\>G | A3252G\-F1 | A3252G\-F1\-I2 | Uninf | F | N | Y | A | 46 | / | / | 10% | 5% (BM) | Migraine, depression, hypothyroidism, hearing loss, weakness |  |
| 2 | 3252 | m.3252A\>G | A3252G\-F1 | A3252G\-F1\-II1 | Fam | M | N | N | A | 7 | / | / | / | / | Healthy |  |
| 3 | 3252 | m.3252A\>G | A3252G\-F1 | A3252G\-F1\-II2 | Fam | F | Y | Y | D | 13 | 42% | / | 78% | 48% (BM) | Migraine, recurrent stroke\-like episodes, photoparoxistic response, epilepsy, exercise intolerance, myopathy, gastro\-intestinal symptoms, hearing loss, decreased vision, cognitive delay, MELAS |  |
| 4 | 3252 | m.3252A\>G | A3252G\-F2 | A3252G\-F2\-I2 | Uninf | F | N | ND | A | 60 | / | / | / | / | Difficulty walking, frequent falls, cerebellar degeneration |  |
| 5 | 3252 | m.3252A\>G | A3252G\-F2 | A3252G\-F2\-II1 | Uninf | F | N | N | A | ND | / | / | / | / | Healthy |  |
| 6 | 3252 | m.3252A\>G | A3252G\-F2 | A3252G\-F2\-II2 | Fam | F | N | Y | D | 44 | / | 50% | / | / | Progressive generalised weakness, spastic paraparesis, dysarthria, stroke\-like episode |  |
| 7 | 3252 | m.3252A\>G | A3252G\-F2 | A3252G\-F2\-III2 | Fam | F | N | N | A | ND | \<3% | 7% | / | 6% (F) | Healthy |  |
| 8 | 3252 | m.3252A\>G | A3252G\-F2 | A3252G\-F2\-III3 | Fam | F | Y | Y | D | 4 | 30% | 76% | / | 76% (Lymphoblast) | Encephalomyopathy, pigmentary retinopathy, dementia, hypoparathyroidism, diabetes mellitus |  |
| 9 | 3252 | m.3252A\>G | A3252G\-F3 | A3252G\-F3\-II1 | De novo | M | Y | Y | A | 14 | 30% | / | / | / | MERRF/MELAS overlapping syndrome |  |

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