G8969A

# **General Information**

| **Position** | **8969** | **Variant** | **m.8969G\>A** | **Locus** | **MT\-ATP6** | **Amino\-AcidChange** | **S148N** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **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.8969G\>A** variant in MT\-ATP6 has been reported in 5 pedigrees. To date, 10 carriers have been reported. Reported mutation loads ranged from 4% to 96%, with a median of 82% overall; affected carriers showed mutation loads from 61% to 96%, with a median of 89%; unaffected carriers showed mutation loads from 4% to 57%, with a median of 18%. The main clinical manifestations among affected carriers included developmental delay, failure to thrive, ADHD, igA nephropathy, leigh syndrome spectrum, mLASA\-plus, mild intellectual disability, poor growth, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 8969 | m.8969G\>A | G8969A\-F1 | Netherlands | mtDNA disease; de novo MT\-ATP6 mutation | 0 | 0 | 2017 | [27450679](https://pubmed.ncbi.nlm.nih.gov/27450679/) |  |
| 2 | 8969 | m.8969G\>A | G8969A\-F2 | USA | MLASA\-plus mitochondrial disease | 0 | 0 | 2014 | [25037980](https://pubmed.ncbi.nlm.nih.gov/25037980/) |  |
| 3 | 8969 | m.8969G\>A | [G8969A\-F3](https://mitofam.com/doc/1763/) | Finland | Mild MT\-ATP6\-associated mitochondrial disease | 3 | 1 | 2018 | [29350304](https://pubmed.ncbi.nlm.nih.gov/29350304/) |  |
| 4 | 8969 | m.8969G\>A | G8969A\-F4 | USA | Leigh syndrome spectrum | 0 | 0 | 2025 | [40241304](https://pubmed.ncbi.nlm.nih.gov/40241304/) |  |
| 5 | 8969 | m.8969G\>A |[ G8969A\-F5](https://mitofam.com/doc/1764/) | China | IgA nephropathy; mitochondrial cytopathy | 1 | 0 | 2016 | [27812026](https://pubmed.ncbi.nlm.nih.gov/27812026/) |  |

# **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 | 8969 | m.8969G\>A | G8969A\-F1 | G8969A\-F1\-II1 | De novo | M | Y | Y | D | 7\.5 months | 95% | 95% | / | 95%(F) | mtDNA disease; de novo MT\-ATP6 mutation |  |
| 2 | 8969 | m.8969G\>A | G8969A\-F2 | G8969A\-F2\-P1 | De novo | M | Y | Y | A | 6 | 96% | 88% | / | 85%(F) | MLASA\-plus; developmental delay; sensorineural hearing loss; epilepsy; agenesis corpus callosum; failure to thrive; stroke\-like episodes |  |
| 3 | 8969 | m.8969G\>A | G8969A\-F3 | G8969A\-F3\-III4 | Fam | F | Y | Y | A | 5 | / | 95% | / | 96%(F) | Poor growth; developmental delay; intellectual disability; elevated lactate |  |
| 4 | 8969 | m.8969G\>A | G8969A\-F3 | G8969A\-F3\-III1 | Fam | M | N | Y | A | 9 | 79% | / | / | / | Mild intellectual disability; ADHD; elevated CSF lactate |  |
| 5 | 8969 | m.8969G\>A | G8969A\-F3 | G8969A\-F3\-III2 | Fam | M | N | N | A | ND | 18% | / | / | / | Healthy |  |
| 6 | 8969 | m.8969G\>A | G8969A\-F3 | G8969A\-F3\-III3 | Fam | M | N | N | A | ND | 4% | / | / | / | Healthy |  |
| 7 | 8969 | m.8969G\>A | G8969A\-F3 | G8969A\-F3\-II9 | Uninf | F | N | N | A | ND | 9% | / | / | / | Healthy |  |
| 8 | 8969 | m.8969G\>A | G8969A\-F4 | G8969A\-F4\-P1 | De novo | ND | Y | Y | ND | ND | / | / | / | 70%(GS sample; tissue NR) | Leigh syndrome spectrum; hypotonia; failure to thrive; episodic vomiting. |  |
| 9 | 8969 | m.8969G\>A | G8969A\-F5 | G8969A\-F5\-II1 | Fam | F | Y | Y | A | 14 | 61% | / | 79% | kidney: 89% | IgA nephropathy; renal relapse/oliguria; epileptic episodes; decreased muscle strength; brain atrophy; severe hearing impairment; Wolff\-Parkinson\-White syndrome; increased fasting glucose. |  |
| 10 | 8969 | m.8969G\>A | G8969A\-F5 | G8969A\-F5\-I2 | Uninf | F | N | N | A | ND | 49% | / | 57% | / | Healthy/asymptomatic. |  |

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