T10191C

# **General Information**

| **Position** | **10191** | **Variant** | **m.10191T\>C** | **Locus** | **MT\-ND3** | **Amino\-AcidChange** | **S45P** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \- | **Heteroplasmy** | \+ | **APOGEE2** | Likely\-pathogenic | **Pathogenicity** | Cfrm \[P] |

"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.10191T\>C** variant in MT\-ND3 has been reported in 25 pedigrees. To date, 30 carriers have been reported. Reported mutation loads ranged from 1% to 100%, with a median of 77% overall; affected carriers showed mutation loads from 2% to 100%, with a median of 86\.1%; unaffected carriers showed mutation loads from 1% to 3%, with a median of 1%. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in urine (16%) than in blood (2%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (77%) than in blood (14%). Similar tissue\-specific differences were observed in 1 additional carriers. The main clinical manifestations among affected carriers included leigh syndrome, seizures, stroke\-like episodes, ataxia, epilepsy, leigh\-like syndrome, vomiting, leigh encephalopathy, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 10191 | m.10191T\>C | T10191C\-F1 | France | Leigh encephalopathy, congenital hypotonia/failure to thrive, myoclonic jerks, pyramidal syndrome, high plasma lactate, putamen MRI lesion | 0 | 0 | 2003 | [14684687](https://pubmed.ncbi.nlm.nih.gov/14684687/) |  |
| 2 | 10191 | m.10191T\>C | T10191C\-F2 | France | Leigh encephalopathy, psychomotor retardation | 0 | 0 | 2003 | [14684687](https://pubmed.ncbi.nlm.nih.gov/14684687/) |  |
| 3 | 10191 | m.10191T\>C | T10191C\-F3 | Australia | Leigh\-like/lethal infantile mitochondrial disease, neonatal hypotonia, hypothermia, bradycardia, respiratory/metabolic acidosis, seizure, postmortem neuronal degeneration | 0 | 0 | 2004 | [14705112](https://pubmed.ncbi.nlm.nih.gov/14705112/) |  |
| 4 | 10191 | m.10191T\>C | T10191C\-F4 | Italy | Leigh syndrome | 0 | 0 | 2004 | [15576045](https://pubmed.ncbi.nlm.nih.gov/15576045/) |  |
| 5 | 10191 | m.10191T\>C | T10191C\-F5 | United Kingdom | Undetermined mitochondrial diseases | ND | ND | 2007 | [24642831](https://pubmed.ncbi.nlm.nih.gov/24642831/) |  |
| 6 | 10191 | m.10191T\>C | T10191C\-F6 | Japan | Leigh syndrome | ND | ND | 2016 | [28429146](https://pubmed.ncbi.nlm.nih.gov/28429146/) |  |
| 7 | 10191 | m.10191T\>C | T10191C\-F7 | Japan | Leigh syndrome | ND | ND | 2016 | [28429146](https://pubmed.ncbi.nlm.nih.gov/28429146/) |  |
| 8 | 10191 | m.10191T\>C | T10191C\-F8 | Japan | Leigh syndrome | ND | ND | 2016 | [28429146](https://pubmed.ncbi.nlm.nih.gov/28429146/) |  |
| 9 | 10191 | m.10191T\>C | T10191C\-F9 | Japan | Leigh syndrome | ND | ND | 2016 | [28429146](https://pubmed.ncbi.nlm.nih.gov/28429146/) |  |
| 10 | 10191 | m.10191T\>C | T10191C\-F10 | Japan | Leigh syndrome | ND | ND | 2016 | [28429146](https://pubmed.ncbi.nlm.nih.gov/28429146/) |  |
| 11 | 10191 | m.10191T\>C | T10191C\-F11 | China | Stroke\-like episodes | ND | ND | 2018 | [30128709](https://pubmed.ncbi.nlm.nih.gov/30128709/) |  |
| 12 | 10191 | m.10191T\>C | T10191C\-F12 | China | Stroke\-like episodes | ND | ND | 2018 | [30128709](https://pubmed.ncbi.nlm.nih.gov/30128709/) |  |
| 13 | 10191 | m.10191T\>C |[ T10191C\-F13](https://mitofam.com/doc/1218/) | United Kingdom | Stroke\-like episodes | 3 | 0 | 2001 | [11456298](https://pubmed.ncbi.nlm.nih.gov/11456298/) |  |
| 14 | 10191 | m.10191T\>C | [T10191C\-F14](https://mitofam.com/doc/1219/) | Israel | Leigh syndrome | 1 | 0 | 2005 | [16023078](https://pubmed.ncbi.nlm.nih.gov/16023078/) |  |
| 15 | 10191 | m.10191T\>C | [T10191C\-F15](https://mitofam.com/doc/1220/) | Sweden | Dystonia | 1 | 0 | 2005 | [16044424](https://pubmed.ncbi.nlm.nih.gov/16044424/) |  |
| 16 | 10191 | m.10191T\>C | T10191C\-F16 | Italy | Epilepsia partialis continua, optic atrophy, recurrent focal motor seizures, mild sensory\-motor deficit | 0 | 0 | 2007 | [17535832](https://pubmed.ncbi.nlm.nih.gov/17535832/) |  |
| 17 | 10191 | m.10191T\>C | T10191C\-F17 | Korea | MELAS, stroke\-like episodes | 0 | 0 | 2009 | [19617458](https://pubmed.ncbi.nlm.nih.gov/19617458/) |  |
| 18 | 10191 | m.10191T\>C | T10191C\-F18 | Poland | Vomiting, hypotony, nystagmus, exacerbation episodes, hyperalaninemia, respiratory alkalosis, transient liver function failure | 0 | 0 | 2009 | [20226758](https://pubmed.ncbi.nlm.nih.gov/20226758/) |  |
| 19 | 10191 | m.10191T\>C | T10191C\-F19 | France | Stroke\-like episodes, dystonia | ND | ND | 2013 | [23847141](https://pubmed.ncbi.nlm.nih.gov/23847141/) |  |
| 20 | 10191 | m.10191T\>C | T10191C\-F20 | France | Dystonia | ND | ND | 2013 | [23847141](https://pubmed.ncbi.nlm.nih.gov/23847141/) | Carrying T10010C |
| 21 | 10191 | m.10191T\>C | T10191C\-F21 | Netherlands | Undetermined mitochondrial diseases | 0 | 0 | 2017 | [27450679](https://pubmed.ncbi.nlm.nih.gov/27450679/) |  |
| 22 | 10191 | m.10191T\>C | T10191C\-F22 | United States | Leigh syndrome | 0 | 0 | 2021 | [34969639](https://pubmed.ncbi.nlm.nih.gov/34969639/) |  |
| 23 | 10191 | m.10191T\>C | T10191C\-F23 | Austria | Leigh\-like syndrome, epilepsy, choreoathetosis, cerebellar ataxia, migraine, mild cognitive impairment, dysautonomia/POTS, small fiber neuropathy, myopathy, lactic acidosis, multis | 0 | 0 | 2023 | [37196589](https://pubmed.ncbi.nlm.nih.gov/37196589/) |  |
| 24 | 10191 | m.10191T\>C | T10191C\-F24 | Japan | Leigh\-like syndrome, headaches, nausea/vomiting, seizures, brainstem and cortical/subcortical/basal ganglia lesions, central scotoma | 0 | 0 | 2024 | [38437941](https://pubmed.ncbi.nlm.nih.gov/38437941/) | Carrying T13336C |
| 25 | 10191 | m.10191T\>C | T10191C\-F25 | Japan | Leigh syndrome | 0 | 0 | 2024 | [38437941](https://pubmed.ncbi.nlm.nih.gov/38437941/) |  |

# **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 | 10191 | m.10191T\>C | T10191C\-F1 | T10191C\-F1\-P1 | De novo | F | Y | Y | ND | Infancy | / | 90% | / | / | Leigh encephalopathy, congenital hypotonia/failure to thrive, myoclonic jerks, pyramidal syndrome |  |
| 2 | 10191 | m.10191T\>C | T10191C\-F2 | T10191C\-F2\-P1 | De novo | M | Y | Y | A | 12 y | / | 80% | / | / | Leigh encephalopathy, psychomotor retardation |  |
| 3 | 10191 | m.10191T\>C | T10191C\-F3 | T10191C\-F3\-P1 | De novo | M | Y | Y | D | 23 d | / | / | / | \>98%(Other tissue) | Leigh\-like/lethal infantile mitochondrial disease, neonatal hypotonia, hypothermia, bradycardia, seizure |  |
| 4 | 10191 | m.10191T\>C | T10191C\-F4 | T10191C\-F4\-P1 | De novo | ND | Y | Y | ND | ND | 50% | 90% | / | 50%(F) | Leigh syndrome |  |
| 5 | 10191 | m.10191T\>C | T10191C\-F5 | T10191C\-F5\-P1 | Fam | F | Y | Y | A | ND | 2% | / | 16% | / | Undetermined mitochondrial diseases |  |
| 6 | 10191 | m.10191T\>C | T10191C\-F6 | T10191C\-F6\-P1 | Uninf | ND | Y | Y | ND | ND | / | / | / | 100%(F) | Leigh syndrome |  |
| 7 | 10191 | m.10191T\>C | T10191C\-F7 | T10191C\-F7\-P1 | Uninf | ND | Y | Y | ND | ND | / | / | / | 69%(F) | Leigh syndrome |  |
| 8 | 10191 | m.10191T\>C | T10191C\-F8 | T10191C\-F8\-P1 | Uninf | ND | Y | Y | ND | ND | / | / | / | / | Leigh syndrome |  |
| 9 | 10191 | m.10191T\>C | T10191C\-F9 | T10191C\-F9\-P1 | Uninf | ND | Y | Y | ND | ND | / | / | / | 100%(F) | Leigh syndrome |  |
| 10 | 10191 | m.10191T\>C | T10191C\-F10 | T10191C\-F10\-P1 | Uninf | ND | Y | Y | ND | ND | 95% | / | / | / | Leigh syndrome |  |
| 11 | 10191 | m.10191T\>C | T10191C\-F11 | T10191C\-F11\-P1 | Uninf | F | Y | Y | ND | 18 y | 55% | / | / | / | Mental retardation, seizures, stroke\-like episodes, ataxia, pyramidal signs, bulbar palsy |  |
| 12 | 10191 | m.10191T\>C | T10191C\-F12 | T10191C\-F12\-P1 | Uninf | F | Y | Y | ND | 16 y | 52% | / | / | / | Seizures, stroke\-like episodes, ataxia, pyramidal signs, bulbar palsy |  |
| 13 | 10191 | m.10191T\>C | T10191C\-F13 | T10191C\-F13\-Ⅰ1 | Uninf | F | N | N | ND | ND | 3% | / | / | / | Healthy |  |
| 14 | 10191 | m.10191T\>C | T10191C\-F13 | T10191C\-F13\-Ⅱ1 | Fam | M | Y | Y | A | 42 y | 14% | 77% | / | / | Epilepsy, stroke\-like episodes, bilateral optic atrophy, cognitive decline, ataxia, peripheral neuropathy |  |
| 15 | 10191 | m.10191T\>C | T10191C\-F13 | T10191C\-F13\-Ⅱ2 | Fam | ND | N | N | ND | Forties | \<1% | / | / | / | Healthy |  |
| 16 | 10191 | m.10191T\>C | T10191C\-F13 | T10191C\-F13\-Ⅱ3 | Fam | ND | N | N | ND | Forties | \<1% | / | / | / | Healthy |  |
| 17 | 10191 | m.10191T\>C | T10191C\-F14 | T10191C\-F14\-Ⅰ1 | Uninf | F | N | ND | A | ND | 5% | / | / | / | Healthy |  |
| 18 | 10191 | m.10191T\>C | T10191C\-F14 | T10191C\-F14\-Ⅱ1 | Fam | M | Y | Y | A | 5 wk | 100% | 100% | / | 50%(H) | Infantile Leigh syndrome, decreased feeding/alertness, bradypnea/apnea, seizures |  |
| 19 | 10191 | m.10191T\>C | T10191C\-F15 | T10191C\-F15\-Ⅰ1 | Uninf | F | N | ND | ND | ND | 36% | / | / | / | Healthy |  |
| 20 | 10191 | m.10191T\>C | T10191C\-F15 | T10191C\-F15\-Ⅱ1 | Fam | F | Y | Y | A | 8\-22 mo | / | 97% | / | 97%(F) | Leigh\-like syndrome, developmental delay, hypotonia, vomiting, feeding problems, dystonia, ophthalmoplegia, seizures |  |
| 21 | 10191 | m.10191T\>C | T10191C\-F16 | T10191C\-F16\-P1 | De novo | M | Y | Y | D | 21 y | / | / | / | 95%(Other tissue) | Epilepsia partialis continua, optic atrophy, recurrent focal motor seizures, mild sensory\-motor deficit |  |
| 22 | 10191 | m.10191T\>C | T10191C\-F17 | T10191C\-F17\-P1 | De novo | F | Y | Y | A | 5 y | Hetero | Hetero | / | / | MELAS/Leigh overlap, intermittent tremor, episodic ataxia, myoclonic seizures, dysarthria, progressive ataxia, stroke\-like episodes, hearing loss |  |
| 23 | 10191 | m.10191T\>C | T10191C\-F18 | T10191C\-F18\-P1 | De novo | M | Y | Y | ND | 4 mo | / | / | / | \+(Other tissue) | Vomiting, hypotony, nystagmus, exacerbation episodes, hyperalaninemia, respiratory alkalosis, transient liver function failure |  |
| 24 | 10191 | m.10191T\>C | T10191C\-F19 | T10191C\-F19\-P1 | Uninf | M | Y | Y | ND | \<1 y | / | / | / | / | CNS psychomotor retardation, ataxia, epilepsy, regression, stroke\-like episodes, dystonia, muscle PEO, optic atrophy, intrauterine growth failure, lipidosis |  |
| 25 | 10191 | m.10191T\>C | T10191C\-F20 | T10191C\-F20\-P1 | Uninf | M | Y | Y | ND | 1\-16 y | / | / | / | / | CNS dystonia and psychomotor retardation, Leigh syndrome | Carrying T10010C |
| 26 | 10191 | m.10191T\>C | T10191C\-F21 | T10191C\-F21\-P1 | De novo | ND | Y | Y | ND | ND | 100% | 100% | / | / | Undetermined mitochondrial diseases |  |
| 27 | 10191 | m.10191T\>C | T10191C\-F22 | T10191C\-F22\-P1 | De novo | ND | Y | Y | ND | 11\.7 y | 50% | / | / | 85%(F) | Leigh syndrome |  |
| 28 | 10191 | m.10191T\>C | T10191C\-F23 | T10191C\-F23\-P1 | De novo | F | Y | Y | A | 32 y | / | / | / | \+(Other tissue) | Leigh\-like syndrome, epilepsy, choreoathetosis, cerebellar ataxia, migraine, mild cognitive impairment, dysautonomia/POTS, myopathy, multisystem involvement |  |
| 29 | 10191 | m.10191T\>C | T10191C\-F24 | T10191C\-F24\-P1 | De novo | F | Y | Y | ND | 6 y | / | / | / | 67%(Other tissue) | Leigh\-like syndrome, headaches, nausea/vomiting, seizures, central scotoma | Carrying T13336C |
| 30 | 10191 | m.10191T\>C | T10191C\-F25 | T10191C\-F25\-P1 | De novo | F | Y | Y | ND | 8 mo | / | / | / | 87\.2%(Other tissue) | Leigh syndrome, poor oral intake, failure to thrive, developmental delay |  |

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