T12706C

# **General Information**

| **Position** | **12706** | **Variant** | **m.12706T\>C** | **Locus** | **MT\-ND5** | **Amino\-AcidChange** | **F124L** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **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.12706T\>C** variant in MT\-ND5 has been reported in 6 pedigrees. To date, 8 carriers have been reported. Reported mutation loads ranged from 3% to 83%, with a median of 48\.5% overall; affected carriers showed mutation loads from 3% to 83%, with a median of 48\.5%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (83%) and urine (47%) than in blood (3%). The main clinical manifestations among affected carriers included fatal Leigh syndrome with sympathetic imbalance and asymmetric brain lesion, leigh, leigh syndrome, leigh\-like syndrome, MELAS, psychomotor retardation, ptosis, stroke\-like episodes, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 12706 | m.12706T\>C | T12706C\-F1 | United Kingdom | Leigh disease with complex I deficiency | 0 | 0 | 2002 | [11938446](https://pubmed.ncbi.nlm.nih.gov/11938446/) |  |
| 2 | 12706 | m.12706T\>C | T12706C\-F2 | France | Leigh\-like encephalopathy with ptosis/ophthalmoplegia | 0 | 0 | 2003 | [14684687](https://pubmed.ncbi.nlm.nih.gov/14684687/) | Patient 6 |
| 3 | 12706 | m.12706T\>C | T12706C\-F3 | ND | Leigh syndrome | 0 | 0 | 2007 | [17317336](https://pubmed.ncbi.nlm.nih.gov/17317336/) | Mother shared haplogroup X2e but mutation absent in blood.; Case G; Text and Figure showing proband positive and mother negative.; ND; affiliations include USA, Ukraine, and France, but patient nationality is not stated. |
| 4 | 12706 | m.12706T\>C | T12706C\-F4 | Australia inferred | Leigh syndrome | 0 | 0 | 2011 | [21364701](https://pubmed.ncbi.nlm.nih.gov/21364701/) | m.12706T\>C LS proband; Table 1; Australia; Melbourne pediatric/diagnostic cohort inferred from affiliations and cohort source. |
| 5 | 12706 | m.12706T\>C | T12706C\-F5 | France | mitochondrial disorder / complex I deficiency | 0 | 0 | 2013 | [23847141](https://pubmed.ncbi.nlm.nih.gov/23847141/) | French cohort m.12706T\>C; Table 1; France; French Mitochondrial Disease Network cohort. |
| 6 | 12706 | m.12706T\>C | [T12706C\-F6 ](https://mitofam.com/doc/1370/)| Czech Republic | MELAS/stroke\-like | 1 | 0 | 2020 | [31996177](https://pubmed.ncbi.nlm.nih.gov/31996177/) | P5 family; Table 1; maternal testing paragraph.; Czech Republic inferred from Czech diagnostic center and patient cohort context. |

# **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 | 12706 | m.12706T\>C | T12706C\-F1 | T12706C\-F1\-P1 | Uninf | M | Y | Y | D | 6 years at presentation; died at 24 years | / | 43% | / | 30%(F) | Leigh\-like syndrome / mitochondrial encephalomyopathy |  |
| 2 | 12706 | m.12706T\>C | T12706C\-F2 | T12706C\-F2\-P1 | De novo | F | Y | Y | A | 16 years | / | 60% | / | / | Ptosis, fatigue, mild motor delay from 1 year, ophthalmoplegia by 5 years, elevated lactate, cerebral peduncle lacuna; normal schooling at 16\. |  |
| 3 | 12706 | m.12706T\>C | T12706C\-F3 | T12706C\-F3\-P1 | De novo | F | Y | Y | D | ND | about 50% | / | / | / | Fatal Leigh syndrome with sympathetic imbalance and asymmetric brain lesion; died of infection, heart failure and multiorgan failure | Blood mutant load read as approximately 50%; exact age not captured in accessible text.; Case description and gel/sequence figure.; Source: Case G |
| 4 | 12706 | m.12706T\>C | T12706C\-F4 | T12706C\-F4\-P1 | Uninf | ND | Y | Y | A | ND | / | 65% | / | / | Leigh syndrome | Table 1; Source: LS proband; Complex I deficiency. |
| 5 | 12706 | m.12706T\>C | T12706C\-F5 | T12706C\-F5\-P1 | Uninf | M | Y | Y | A | 1\-16 years | / | / | / | / | Psychomotor retardation; epilepsy; ataxia; optic atrophy; deafness; postnatal growth retardation; Leigh/stroke\-like/cerebellar atrophy | Anonymous aggregate row.; Table 1; Source: aggregate patient 1; Decreased complex I in muscle; normal fibroblasts. |
| 6 | 12706 | m.12706T\>C | T12706C\-F5 | T12706C\-F5\-P2 | Uninf | M | Y | Y | A | \>16 years | / | / | / | / | Stroke\-like episodes; encephalopathy | Anonymous aggregate row.; Table 1; Source: aggregate patient 2; Decreased CI\+III in muscle and decreased CI in fibroblasts. |
| 7 | 12706 | m.12706T\>C | T12706C\-F6 | T12706C\-F6\-II1 | Fam | ND | Y | Y | D | onset 17 y; died 42 y | 3% | 83% | 47% | / | Wernicke aphasia; MELAS/stroke\-like phenotype | Table 1 and text.; Source: P5 |
| 8 | 12706 | m.12706T\>C | T12706C\-F6 | T12706C\-F6\-I2 | Fam | F | N | N | A | ND | / | / | / | Positive(ND) | Healthy | Same mtDNA mutation found in mother of P5\.; Results text: six mothers including P5 were positive.; Source: P5 mother |

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