G8328A

# **General Information**

| **Position** | **8328** | **Variant** | **m.8328G\>A** | **Locus** | **MT\-TK** | **RNA** | **tRNA Lys** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **mitoTIP** | 83\.30% | **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.8328G\>A** variant in MT\-TK has been reported in 3 pedigrees. To date, 4 carriers have been reported. Reported mutation loads ranged from 0% to 95\.4%, with a median of 10% overall; affected carriers showed mutation loads from 0% to 95\.4%, with a median of 13%; unaffected carriers showed mutation loads from 0%, with a median of 0%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in deltoid (57%), quadriceps (52%), cox\-positive muscle fibers (59%), and cox\-negative muscle fibers (95%) than in blood (10%). In one affected carrier, the mutation was undetectable in blood (0%), urine (0%), and bone marrow (0%) but exceeded 20% in muscle (82%), other tissue (95\.4%), and other tissue (43\.7%). The main clinical manifestations among affected carriers included exercise intolerance, hypotonia, mitochondrial encephalomyopathy, aerophagia, asthma, bilateral ptosis, cerebellar dysfunction, chronic constipation, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 8328 | m.8328G\>A | [G8328A\-F1](https://mitofam.com/doc/2198/) | Sweden | Encephalopathy / multi\-symptom mitochondrial disease | 1 | 0 | 1999 | [10090475](https://pubmed.ncbi.nlm.nih.gov/10090475/) | Fig. 3 pedigree of investigated family |
| 2 | 8328 | m.8328G\>A | G8328A\-F2 | United Kingdom | Mitochondrial myopathy with exercise intolerance | 0 | 0 | 2007 | [17410322](https://pubmed.ncbi.nlm.nih.gov/17410322/) | / |
| 3 | 8328 | m.8328G\>A | G8328A\-F3 | Unknown | Encephalopathy / EXIT with myopathy and ptosis; multi\-symptom pt | 0 | 0 | 2025 | [40241304](https://pubmed.ncbi.nlm.nih.gov/40241304/) | / |

# **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 | 8328 | m.8328G\>A | G8328A\-F1 | G8328A\-F1\-II1 | Fam | F | N | N | A | 22 | 0 | 0 | / | / | Healthy; no CNS or neuromuscular disease; muscle biopsy normal | Negative\-tested child of target\-positive mother; counted as G. |
| 2 | 8328 | m.8328G\>A | G8328A\-F1 | G8328A\-F1\-II2 | De novo | F | Y | Y | A | 49 | 10% | 57% (deltoid); 52% (quadriceps) | / | 13% (F); 59% (COX\-positive muscle fibers); 95% (COX\-negative muscle fibers) | Mitochondrial encephalomyopathy; impaired balance; migraine; hearing loss; cerebellar dysfunction; retinal degeneration; optic atrophy; cognitive decline | De novo; mother, daughter and siblings tested negative in available samples. |
| 3 | 8328 | m.8328G\>A | G8328A\-F2 | G8328A\-F2\-P1 | De novo | M | Y | Y | A | 59 | 0 | 82% | 0 | 0 (BM); 95\.4\+/\-1\.2% (COX\-deficient fibers); 43\.7\+/\-8\.4% (COX\-positive fibers) | Exercise intolerance; bilateral ptosis; proximal muscle weakness; mild sensorimotor axonal neuropathy | Sporadic/de novo; mutation undetectable in blood, BM and urine from patient and mother. |
| 4 | 8328 | m.8328G\>A | G8328A\-F3 | G8328A\-F3\-P1 | De novo | ND | Y | Y | ND | ND | / | / | / | 6% (ND) | Hypotonia; stridor; feeding difficulties; laryngomalacia; chronic constipation; fatigue; disturbed sleep; aerophagia; reflux; asthma; periodic limb movement; muscle fatigue; loss of skill; plagiocephaly; neck flexion weakness | Original proband ID P18; ACMG VUS candidate; GS sample 6% (537/8952\); sample tissue, sex and age not reported in main Table 2\. |

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