T8528C

# **General Information**

| **Position** | **8528** | **Variant** | **m.8528T\>C** | **Locus** | **MT\-ATP8/6** | **Amino\-AcidChange** | **ATP8:W55R ATP6:M1T** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **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.8528T\>C** variant in MT\-ATP8/6 has been reported in 8 pedigrees. To date, 12 carriers have been reported. Homoplasmy was reported in 4/12 carriers (33\.3%), and 9/12 carriers (75%) were affected. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in blood (59%) than in fibroblasts (15%). The main clinical manifestations among affected carriers included infantile hypertrophic cardiomyopathy, hypertrophic cardiomyopathy, hypotonia, hyperammonemia, lactic acidosis, motor delay, infantile mitochondrial disease, LVNC, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 8528 | m.8528T\>C | [T8528C\-F1](https://mitofam.com/doc/1854/) | United States | Infantile hypertrophic cardiomyopathy | 1 | 0 | 2009 | [19188198](https://pubmed.ncbi.nlm.nih.gov/19188198/) |  |
| 2 | 8528 | m.8528T\>C | T8528C\-F2 | United States | Infantile hypertrophic cardiomyopathy | 0 | 0 | 2009 | [19188198](https://pubmed.ncbi.nlm.nih.gov/19188198/) |  |
| 3 | 8528 | m.8528T\>C | T8528C\-F3 | United States | Infantile hypertrophic cardiomyopathy | 0 | 0 | 2009 | [19188198](https://pubmed.ncbi.nlm.nih.gov/19188198/) |  |
| 4 | 8528 | m.8528T\>C | [T8528C\-F4](https://mitofam.com/doc/1855/) | United States | Infantile hypertrophic cardiomyopathy | 0 | 1 | 2009 | [19188198](https://pubmed.ncbi.nlm.nih.gov/19188198/) |  |
| 5 | 8528 | m.8528T\>C |[ T8528C\-F5](https://mitofam.com/doc/1856/) | Japan | Rapidly progressive infantile cardiomyopathy | 1 | 0 | 2016 | [26803244](https://pubmed.ncbi.nlm.nih.gov/26803244/) |  |
| 6 | 8528 | m.8528T\>C | [T8528C\-F8](https://mitofam.com/doc/1857/) | Croatia | ATP synthase deficiency with neonatal hyperammonemia and cardiomyopathy | 1 | 0 | 2021 | [33180048](https://pubmed.ncbi.nlm.nih.gov/33180048/) |  |
| 7 | 8528 | m.8528T\>C | T8528C\-F6 | Japan | Mitochondrial cardiomyopathy | 1 | 0 | 2021 | [34298071](https://pubmed.ncbi.nlm.nih.gov/34298071/) |  |
| 8 | 8528 | m.8528T\>C | T8528C\-F7 | Japan | Infantile mitochondrial disease with cardiomyopathy | 0 | 0 | 2021 | [34298071](https://pubmed.ncbi.nlm.nih.gov/34298071/) |  |

# **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 | 8528 | m.8528T\>C | T8528C\-F1 | T8528C\-F1\-II1 | Fam | F | Y | Y | A | 6wk | 98% | 98% | / | 93%(F); 93%(BM); 92%(H) | Infantile hypertrophic cardiomyopathy; LVNC; hypotonia; feeding difficulty; motor delay |  |
| 2 | 8528 | m.8528T\>C | T8528C\-F1 | T8528C\-F1\-I2 | Uninf | F | N | N | A | ND | 16% | / | 25% | 25%(F); 20%(BM); 18%(H) | Healthy |  |
| 3 | 8528 | m.8528T\>C | T8528C\-F2 | T8528C\-F2\-II1 | Uninf | M | Y | Y | A | 5mo | Homo | / | / | / | Infantile hypertrophic cardiomyopathy; congestive heart failure; failure to thrive; arrhythmia |  |
| 4 | 8528 | m.8528T\>C | T8528C\-F3 | T8528C\-F3\-II1 | Uninf | M | Y | Y | A | 1wk | Homo | Homo | / | Homo(F); Homo(Liver) | Infantile hypertrophic cardiomyopathy; pericardial effusion; liver involvement; hyperammonemia; motor delay |  |
| 5 | 8528 | m.8528T\>C | T8528C\-F4 | T8528C\-F4\-II2 | Uninf | F | Y | Y | A | prenatal | Homo | Homo | / | / | Infantile hypertrophic cardiomyopathy; pulmonary hypertension; thrombocytopenia; hypotonia |  |
| 6 | 8528 | m.8528T\>C | T8528C\-F4 | T8528C\-F4\-II1 | Fam | F | N | Y | D | 1mo | \+ | \+ | / | / | Infantile hypertrophic cardiomyopathy; lactic acidosis; respiratory failure |  |
| 7 | 8528 | m.8528T\>C | T8528C\-F5 | T8528C\-F5\-II1 | Fam | F | Y | Y | D | 5\.5mo | 88% | / | / | 90%(Heart); 86%(F) | Rapidly progressive infantile cardiomyopathy; biventricular hypertrophy; metabolic acidosis; hyperammonemia; hyperlactacidemia |  |
| 8 | 8528 | m.8528T\>C | T8528C\-F5 | T8528C\-F5\-I2 | Uninf | F | N | N | A | ND | / | / | / | 1\.4%(F) | Healthy |  |
| 9 | 8528 | m.8528T\>C | T8528C\-F8 | T8528C\-F8\-II1 | Fam | F | Y | Y | D | 2\.5mo | Homo | / | / | / | Neonatal hyperammonemia; hypertrophic cardiomyopathy; lactic acidosis; hypotonia; nystagmus |  |
| 10 | 8528 | m.8528T\>C | T8528C\-F8 | T8528C\-F8\-I2 | Uninf | F | N | N | A | ND | 82% | / | 89% | 59%(Saliva) | Almost asymptomatic; short stature; migraines; microprolactinoma; miscarriages |  |
| 11 | 8528 | m.8528T\>C | T8528C\-F6 | T8528C\-F6\-II1 | Fam | F | Y | Y | D | 2mo | 88% | 91% | / | 90%(Heart); 86%(F); 88%(Liver) | Mitochondrial cardiomyopathy; hypertrophic cardiomyopathy; onset day 2 |  |
| 12 | 8528 | m.8528T\>C | T8528C\-F7 | T8528C\-F7\-II1 | Uninf | M | Y | Y | A | 2y8m | 59% | / | / | 15%(F) | Infantile mitochondrial disease; hypertrophic cardiomyopathy; poor weight gain |  |

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