C11777A

# **General Information**

| **Position** | **11777** | **Variant** | **m.11777C\>A** | **Locus** | **MT\-ND4** | **Amino\-AcidChange** | **R340S** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **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.11777C\>A** variant in MT\-ND4 has been reported in 7 pedigrees. To date, 10 carriers have been reported. Reported mutation loads ranged from 3% to 93%, with a median of 55\.5% overall; affected carriers showed mutation loads from 40% to 93%, with a median of 67%; unaffected carriers showed mutation loads from 3% to 54%, with a median of 28\.5%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (83%) than in blood (40%). The main clinical manifestations among affected carriers included leigh syndrome, complex I deficiency, high lactate, lactic acidosis, seizures, encephalopathy, mRI brainstem lesions, severe Leigh syndrome, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 11777 | m.11777C\>A | C11777A\-F1 | Germany | Mitochondrial encephalopathy; complex I deficiency | ND | ND | 2003 | [12707444](https://pubmed.ncbi.nlm.nih.gov/12707444/) |  |
| 2 | 11777 | m.11777C\>A | C11777A\-F2 | Italy | Leigh syndrome; complex I deficiency | ND | ND | 2004 | [15576045](https://pubmed.ncbi.nlm.nih.gov/15576045/) |  |
| 3 | 11777 | m.11777C\>A | C11777A\-F3 | Japan | Singleton; de novo supported | ND | ND | 2003 | [16120329](https://pubmed.ncbi.nlm.nih.gov/16120329/) |  |
| 4 | 11777 | m.11777C\>A | C11777A\-F4 | Japan | Singleton; maternal status unavailable | ND | ND | 2003 | [16120329](https://pubmed.ncbi.nlm.nih.gov/16120329/) |  |
| 5 | 11777 | m.11777C\>A | [C11777A\-F5](https://mitofam.com/doc/1878/) | Hungary | Leigh syndrome | 1 | 0 | 2010 | [20502985](https://pubmed.ncbi.nlm.nih.gov/20502985/) |  |
| 6 | 11777 | m.11777C\>A | [C11777A\-F6 ](https://mitofam.com/doc/1879/)| United Kingdom | Prenatal mitochondrial disease testing | 0 | 0 | 2014 | [24642831](https://pubmed.ncbi.nlm.nih.gov/24642831/) |  |
| 7 | 11777 | m.11777C\>A | [C11777A\-F7](https://mitofam.com/doc/1880/) | United Kingdom | Prenatal mitochondrial disease testing | 1 | 0 | 2014 | [24642831](https://pubmed.ncbi.nlm.nih.gov/24642831/) |  |

# **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 | 11777 | m.11777C\>A | C11777A\-F1 | C11777A\-F1\-P1 | Uninf | M | Y | Y | D | 67 | / | 93% | / | 67%(brain cerebellum/midbrain); 81%(hippocampus); 69%(gyrus frontalis) | Encephalopathy; seizures; lactic acidosis; stroke\-like brain lesions; complex I deficiency | Original ID: Patient died |
| 2 | 11777 | m.11777C\>A | C11777A\-F2 | C11777A\-F2\-P1 | Uninf | ND | Y | Y | ND | ND | / | 60% | / | / | Severe Leigh syndrome; lactic acidosis; increased CSF lactate; complex I deficiency | Original ID: Patient 2 |
| 3 | 11777 | m.11777C\>A | C11777A\-F3 | C11777A\-F3\-P1 | De novo | F | Y | Y | ND | 4 | 40% | 83% | / | 78%(myoblast); 57%(F) | Leigh syndrome; developmental delay; ataxia; high lactate; basal ganglia lesions |  |
| 4 | 11777 | m.11777C\>A | C11777A\-F4 | C11777A\-F4\-P1 | Uninf | F | Y | Y | ND | 5 | 52% | 76% | / | 76%(myoblast) | Leigh syndrome; developmental delay and deterioration; dystonia; high lactate |  |
| 5 | 11777 | m.11777C\>A | C11777A\-F5 | C11777A\-F5\-IV1 | Fam | M | Y | Y | D | 17 months | 50% | 60% | / | 60%(Liver) | Leigh syndrome; myoclonus day 5; seizures, cerebral paresis and hypotonia; MRI brainstem lesions; cardiorespiratory arrest |  |
| 6 | 11777 | m.11777C\>A | C11777A\-F5 | C11777A\-F5\-III1 | Fam | F | N | N | A | ND | \<3% | / | / | / | Healthy |  |
| 7 | 11777 | m.11777C\>A | C11777A\-F6 | C11777A\-F6\-II1 | Fam | ND | N | ND | ND | gestation NR | / | / | / | 46%(CVB) | ND |  |
| 8 | 11777 | m.11777C\>A | C11777A\-F6 | C11777A\-F6\-I1 | Uninf | F | Y | ND | A | ND | 30% | / | 36% | 43%(BM) | ND |  |
| 9 | 11777 | m.11777C\>A | C11777A\-F7 | C11777A\-F7\-II1 | Fam | ND | N | N | A | 5 years | / | / | / | 54%(CVB) | Healthy |  |
| 10 | 11777 | m.11777C\>A | C11777A\-F7 | C11777A\-F7\-I1 | Uninf | F | Y | ND | A | ND | 18% | / | 32% | 20%(BM) | ND |  |

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