G14453A

# **General Information**

| **Position** | **14453** | **Variant** | **m.14453G\>A** | **Locus** | **MT\-ND6** | **Amino\-AcidChange** | **A74V** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **APOGEE2** | Likely\-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.14453G\>A** variant in MT\-ND6 has been reported in 8 pedigrees. To date, 9 carriers have been reported. Reported mutation loads ranged from 2% to 83%, with a median of 73% overall; affected carriers showed mutation loads from 41% to 83%, with a median of 73\.5%. The main clinical manifestations among affected carriers included infantile LS, seizures, ataxia, hyperlactatemia, hypotonia, leigh syndrome, developmental delay, lactic acidosis, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 14453 | m.14453G\>A | G14453A\-F1 | Denmark | MELAS syndrome | 0 | 0 | 2001 | [11781695](https://pubmed.ncbi.nlm.nih.gov/11781695/) |  |
| 2 | 14453 | m.14453G\>A | G14453A\-F2 | Australia | Leigh syndrome | 0 | 0 | 2011 | [21364701](https://pubmed.ncbi.nlm.nih.gov/21364701/) |  |
| 3 | 14453 | m.14453G\>A | G14453A\-F3 | Japan | MELAS | 0 | 0 | 2020 | [32552696](https://pubmed.ncbi.nlm.nih.gov/32552696/) |  |
| 4 | 14453 | m.14453G\>A | G14453A\-F4 | Japan | Leigh syndrome and mitochondrial cardiomyopathy | 0 | 0 | 2021 | [33644659](https://pubmed.ncbi.nlm.nih.gov/33644659/) |  |
| 5 | 14453 | m.14453G\>A | G14453A\-F5 | Japan | Leigh syndrome | 0 | 0 | 2022 | [34933128](https://pubmed.ncbi.nlm.nih.gov/34933128/) |  |
| 6 | 14453 | m.14453G\>A | G14453A\-F6 | Japan | Leigh syndrome | 0 | 0 | 2022 | [34933128](https://pubmed.ncbi.nlm.nih.gov/34933128/) |  |
| 7 | 14453 | m.14453G\>A | G14453A\-F7 | Japan | Leigh syndrome | 0 | 0 | 2022 | [34933128](https://pubmed.ncbi.nlm.nih.gov/34933128/) |  |
| 8 | 14453 | m.14453G\>A | G14453A\-F8 | Japan | Leigh syndrome | 0 | 0 | 2022 | [34933128](https://pubmed.ncbi.nlm.nih.gov/34933128/) |  |

# **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 | 14453 | m.14453G\>A | G14453A\-F1 | G14453A\-F1\-P1 | Uninf | F | Y | Y | ND | 7 y | 78%; Guthrie card 75% | 82% | / | / | MELAS syndrome; normal until age 2 y; vomiting with ketotic acidosis; myoclonic epilepsy; seizures; weakness; ataxia; intermittent dystonia; lactic acidosis; stroke\-like episodes; multi\-infarctions; no optic nerve atrophy |  |
| 2 | 14453 | m.14453G\>A | G14453A\-F2 | G14453A\-F2\-P1 | Uninf | ND | Y | Y | ND | ND | / | / | / | 41% (F) | Leigh syndrome |  |
| 3 | 14453 | m.14453G\>A | G14453A\-F3 | G14453A\-F3\-P1 | Uninf | M | Y | Y | A | 74 | / | 53% | / | / | acute encephalitis\-like MELAS; cognitive impairment; psychosis; seizures; left hemiparesis | co\-reported D\-loop variants 189A\>G and 16129G\>A |
| 4 | 14453 | m.14453G\>A | G14453A\-F4 | G14453A\-F4\-P1 | De novo | M | Y | Y | A | 17 | 60% | / | / | 83% (cardiac tissue) | Leigh syndrome; mitochondrial cardiomyopathy; delayed motor development; metabolic acidosis; seizures |  |
| 5 | 14453 | m.14453G\>A | G14453A\-F5 | G14453A\-F5\-P1 | Uninf | M | Y | Y | D | 3 y 3 m | / | / | / | 51%(F); 75%(cardiac muscle) | Infantile LS; hypotonia; lactic acidosis; HCM with cardiac failure; seizures; brainstem and basal ganglia lesions; chronic anemia | Original label Pt0322 |
| 6 | 14453 | m.14453G\>A | G14453A\-F6 | G14453A\-F6\-P1 | De novo | F | Y | Y | D | 6 y 11 m | 74% | 83% | / | 44%(F) | Infantile LS; failure to thrive; hypertension; WPW; ataxia; regression; strabismus; hypotonia; hyperlactatemia; putamen and midbrain lesions | Original label Pt1315 |
| 7 | 14453 | m.14453G\>A | G14453A\-F7 | G14453A\-F7\-P1 | Fam | M | Y | Y | A | 3 y 4 m | 79% | / | / | 73%(F) | Infantile LS; developmental delay; hypotonia; epilepsy; poor feeding and growth restriction; hyperlactatemia; basal ganglia and brainstem lesions; ptosis and strabismus | Original label Pt2378 |
| 8 | 14453 | m.14453G\>A | G14453A\-F7 | G14453A\-F7\-P2 | Fam | F | N | ND | ND | ND | 2% | / | / | / | Phenotype not reported |  |
| 9 | 14453 | m.14453G\>A | G14453A\-F8 | G14453A\-F8\-P1 | De novo | F | Y | Y | A | 9 y | 52% | / | / | 57%(F) | Infantile LS; developmental delay; dysarthria; stutter; dystonia; ataxia; hyperlactatemia; putamen and midbrain lesions; cerebellar atrophy | Original label Pt2794 |

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