T8357C

# **General Information**

| **Position** | **8357** | **Variant** | **m.8357T\>C** | **Locus** | **MT\-TK** | **RNA** | **tRNA Lys** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **mitoTIP** | 59\.10% | **Pathogenicity** | Reported |

"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.8357T\>C** variant in MT\-TK has been reported in 2 pedigrees. To date, 10 carriers have been reported. Reported mutation loads ranged from 36% to 100%, with a median of 96\.5% overall; affected carriers showed mutation loads from 38% to 100%, with a median of 98%; unaffected carriers showed mutation loads from 36% to 78%, with a median of 48%. The main clinical manifestations among affected carriers included facial dysmorphisms, mild intellectual disability, mild neurosensory hearing impairment, anemia, bone marrow hypocellularity, clumsiness, decreased mitochondrial complex I, delayed speech and language, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 8357 | m.8357T\>C | [T8357C\-F1 ](https://mitofam.com/doc/2221/)| Venezuela | Multiple symmetric lipomatosis; dermatologic manifestations | 1 | 2 | 2020 | [31912494](https://pubmed.ncbi.nlm.nih.gov/31912494/) | / |
| 2 | 8357 | m.8357T\>C | [T8357C\-F2](https://mitofam.com/doc/2222/) | Italian | Multiorgan mitochondrial disease | 2 | 3 | 2025 | [40834966](https://pubmed.ncbi.nlm.nih.gov/40834966/) | / |

# **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 | 8357 | m.8357T\>C | T8357C\-F1 | T8357C\-F1\-II1 | Fam | F | N | Y | A | ND | 43% | / | / | / | Abdominal and shoulder lipomas; osteoarthritis; herniated disc; controlled arterial hypertension | Mother of proband. |
| 2 | 8357 | m.8357T\>C | T8357C\-F1 | T8357C\-F1\-III1 | Fam | M | Y | Y | A | 47 | 53%; 65% | / | / | / | Multiple symmetric lipomatosis; erythematous\-scaly pruritic plaques; hand hyperkeratosis; desquamative lesions on right thumb and index; brachycephaly; facial asymmetry; degenerative discopathy; bilateral microlithiasis; sporadic elevation of blood pressure; hyperuricemia; mixed dyslipidemia | Two blood samples from proband. |
| 3 | 8357 | m.8357T\>C | T8357C\-F1 | T8357C\-F1\-III2 | Fam | F | N | Y | A | ND | 38% | / | / | / | Abdominal lipoma\-type lesions | Maternal half sister. |
| 4 | 8357 | m.8357T\>C | T8357C\-F1 | T8357C\-F1\-III3 | Fam | M | N | N | A | ND | / | / | / | / | Healthy | Maternal half brother III\-3; no molecular testing; clinically healthy. |
| 5 | 8357 | m.8357T\>C | T8357C\-F2 | T8357C\-F2\-I1 | Uninf | F | N | N | A | 53 | 56% | / | 78% | / | Healthy; frequent labyrinthitis episodes | / |
| 6 | 8357 | m.8357T\>C | T8357C\-F2 | T8357C\-F2\-II1 | Fam | F | N | Y | A | 32 | 84% | / | 94% | 81% (F); 97% (F) | Mild neurosensory hearing impairment | / |
| 7 | 8357 | m.8357T\>C | T8357C\-F2 | T8357C\-F2\-II2 | Fam | F | N | Y | A | 24 | 96% | / | 99% | / | Mild intellectual disability; clumsiness; exercise\-induced muscle fatigue; action tremor; anxiety; mild neurosensory hearing impairment | / |
| 8 | 8357 | m.8357T\>C | T8357C\-F2 | T8357C\-F2\-II3 | Fam | M | N | N | A | ND | 36% | / | 40% | / | Healthy | / |
| 9 | 8357 | m.8357T\>C | T8357C\-F2 | T8357C\-F2\-III1 | Fam | M | Y | Y | A | 10 | 100% | 100% | 99% | 98% (F); 98% (F) | Facial dysmorphisms; mild intellectual disability; delayed speech and language; clumsiness; exercise\-induced muscle fatigue; abnormal EEG; progressive sensorineural hearing impairment; lactic acidosis; metabolic acidosis; hyperkalemia; hepatic steatosis; anemia; bone marrow hypocellularity; decreased mitochondrial complex I | / |
| 10 | 8357 | m.8357T\>C | T8357C\-F2 | T8357C\-F2\-III2 | Fam | F | N | Y | A | 7 | 100% | 100% | 99% | 99% (F); 98% (F) | Facial dysmorphisms; intrauterine growth restriction; oligohydramnios; failure to thrive; delayed speech and language; absence seizure with eyelid myoclonus; moderate sensorineural hearing impairment; lactic acidosis; metabolic acidosis; hyperkalemia; anemia; bone marrow hypocellularity; decreased mitochondrial complex I | / |

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