T8356C

# **General Information**

| **Position** | **8356** | **Variant** | **m.8356T\>C** | **Locus** | **MT\-TK** | **RNA** | **tRNA Lys** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **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.8356T\>C** variant in MT\-TK has been reported in 3 pedigrees. To date, 22 carriers have been reported. Homoplasmy was reported in 3/22 carriers (13\.6%), and 13/22 carriers (59\.1%) were affected. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (homoplasmy) than in blood (47%). In one affected carrier, the mutation was undetectable in blood (0%) but exceeded 20% in muscle (45\.2%). Similar tissue\-specific differences were observed in 3 additional carriers. The main clinical manifestations among affected carriers included MERRF, hearing loss, myoclonic epilepsy, euthyroid goiter, neural deafness, ataxia, mild neural deafness, RRF, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 8356 | m.8356T\>C | T8356C\-F1 | USA | MERRF | 0 | 5 | 1992 | [1361099](https://pubmed.ncbi.nlm.nih.gov/1361099/) | Figure 1 pedigree |
| 2 | 8356 | m.8356T\>C |[ T8356C\-F2](https://mitofam.com/doc/2218/) | Italy | MERRF/MELAS overlap syndrome | 4 | 6 | 1993 | [8069654](https://pubmed.ncbi.nlm.nih.gov/8069654/) | / |
| 3 | 8356 | m.8356T\>C | [T8356C\-F3](https://mitofam.com/doc/2219/) | Japan | MERRF/MELAS overlap | 8 | 5 | 2010 | [20610441](https://pubmed.ncbi.nlm.nih.gov/20610441/) | / |

# **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 | 8356 | m.8356T\>C | T8356C\-F1 | T8356C\-F1\-III12 | Fam | F | Y | Y | A | 36 | 47% | Homo | / | / | MERRF; myoclonic epilepsy; generalized seizures; ataxia; myopathy; hearing loss; lactic acidosis; ragged\-red fibers | Patient 5 (III\-12\) |
| 2 | 8356 | m.8356T\>C | T8356C\-F2 | T8356C\-F2\-I1 | Uninf | F | N | Y | A | 54 | / | 87\.5% | / | / | Neural deafness; cataract; myoclonus; ataxia; dementia | Original label I\-1; lymphocyte mutant mtDNA barely detectable |
| 3 | 8356 | m.8356T\>C | T8356C\-F2 | T8356C\-F2\-II1 | Fam | M | N | N | A | 30 | / | / | / | / | Healthy | Original label II\-1 |
| 4 | 8356 | m.8356T\>C | T8356C\-F2 | T8356C\-F2\-II2 | Fam | F | N | Y | D | 32 | / | / | / | / | Stroke\-like episodes; massive cerebral stroke; myoclonus epilepsy; neural deafness; severe ataxia; migrainous attacks; dementia | Original label II\-2 |
| 5 | 8356 | m.8356T\>C | T8356C\-F2 | T8356C\-F2\-II3 | Fam | M | N | N | A | 27 | 0 | 0 | / | / | Healthy | Original label II\-3 |
| 6 | 8356 | m.8356T\>C | T8356C\-F2 | T8356C\-F2\-II4 | Fam | F | N | Y | A | 23 | 0 | 45\.2% | / | / | Mild neural deafness | Original label II\-4 |
| 7 | 8356 | m.8356T\>C | T8356C\-F2 | T8356C\-F2\-II5 | Fam | F | N | Y | A | 21 | / | / | / | / | Euthyroid goiter | Original label II\-5 |
| 8 | 8356 | m.8356T\>C | T8356C\-F2 | T8356C\-F2\-II6 | Fam | M | N | N | A | 23 | 0 | 56\.7% | / | / | Healthy; EEG abnormalities | Original label II\-6 |
| 9 | 8356 | m.8356T\>C | T8356C\-F2 | T8356C\-F2\-II7 | Fam | F | N | Y | A | 17 | 0 | 43\.4% | / | / | Deafness; euthyroid goiter | Original label II\-7 |
| 10 | 8356 | m.8356T\>C | T8356C\-F2 | T8356C\-F2\-II8 | Fam | F | N | Y | A | 16 | / | 56\.7% | / | / | Migrainous attacks; myoclonus epilepsy; neural deafness; euthyroid goiter | Original label II\-8; lymphocyte mutant mtDNA barely detectable |
| 11 | 8356 | m.8356T\>C | T8356C\-F2 | T8356C\-F2\-II9 | Fam | M | N | N | A | 9 | 0 | 47\.1% | / | / | Healthy; EEG abnormalities | Original label II\-9 |
| 12 | 8356 | m.8356T\>C | T8356C\-F2 | T8356C\-F2\-III1 | Fam | M | Y | Y | A | 11 | / | 84\.4% | / | / | Severe myoclonus epilepsy; cerebellar ataxia; mild neural deafness | Original label III\-1; lymphocyte mutant mtDNA barely detectable; elevated lactate/CK |
| 13 | 8356 | m.8356T\>C | T8356C\-F3 | T8356C\-F3\-II1 | Fam | F | N | N | A | 51 | Hetero; load low NR | / | / | / | Healthy | m.8356T\>C and m.3243A\>G detected in blood; lowest load among tested relatives. |
| 14 | 8356 | m.8356T\>C | T8356C\-F3 | T8356C\-F3\-II2 | Fam | F | N | Y | D | 45; died 46 | Hetero; load NR | Homo | / | / | MERRF/MELAS overlap; hearing loss; myoclonic epilepsy; stroke\-like episodes; elevated lactate; RRF; SSV; renal and heart failure | Muscle m.8356T\>C appeared homoplasmic by RFLP; also carried m.3243A\>G. |
| 15 | 8356 | m.8356T\>C | T8356C\-F3 | T8356C\-F3\-III1 | Fam | F | Y | Y | A | 23 | Hetero; load NR | Homo | / | / | MERRF; hearing loss; myoclonic epilepsy; ataxia; RRF; SSV; high CSF lactate | Onset at 17; also carried m.3243A\>G. |
| 16 | 8356 | m.8356T\>C | T8356C\-F3 | T8356C\-F3\-III2 | Fam | M | N | N | A | ND | / | / | / | / | Healthy | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported. |
| 17 | 8356 | m.8356T\>C | T8356C\-F3 | T8356C\-F3\-III3 | Fam | M | N | N | A | ND | / | / | / | / | Healthy | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported. |
| 18 | 8356 | m.8356T\>C | T8356C\-F3 | T8356C\-F3\-III4 | Fam | M | N | N | A | ND | / | / | / | / | Healthy | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported. |
| 19 | 8356 | m.8356T\>C | T8356C\-F3 | T8356C\-F3\-III5 | Fam | F | N | Y | A | ND | / | / | / | / | Hearing loss; mental retardation | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported. |
| 20 | 8356 | m.8356T\>C | T8356C\-F3 | T8356C\-F3\-III6 | Fam | F | N | Y | A | 21 | Hetero; load NR | / | / | / | MERRF; myoclonic epilepsy; cerebellar ataxia; elevated lactate; no deafness | Blood heteroplasmy for m.8356T\>C and m.3243A\>G. |
| 21 | 8356 | m.8356T\>C | T8356C\-F3 | T8356C\-F3\-III7 | Fam | M | N | Y | D | 1 | / | / | / | / | Sudden death at 1 year | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported. |
| 22 | 8356 | m.8356T\>C | T8356C\-F3 | T8356C\-F3\-III8 | Fam | M | N | N | A | ND | / | / | / | / | Healthy | No molecular testing in child; included because mother has confirmed mutation load and child phenotype is explicitly reported. |

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