T10158C

# **General Information**

| **Position** | **10158** | **Variant** | **m.10158T\>C** | **Locus** | **MT\-ND3** | **Amino\-AcidChange** | **S34P** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **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.10158T\>C** variant in MT\-ND3 has been reported in 20 pedigrees. To date, 23 carriers have been reported. Homoplasmy was reported in 1/23 carriers (4\.3%), and 19/23 carriers (82\.6%) were affected. In one affected carrier, the mutation was undetectable in blood (0%) but exceeded 20% in muscle (85%). In one affected carrier, the mutation was undetectable in blood (0%) but exceeded 20% in muscle (85%). Similar tissue\-specific differences were observed in 2 additional carriers. The main clinical manifestations among affected carriers included leigh syndrome, seizures, leigh disease, leigh encephalopathy, MELAS, bulbar palsy, dysarthria, failure to thrive, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 10158 | m.10158T\>C | T10158C\-F1 | France | Leigh disease | 0 | 0 | 2003 | [14684687](https://pubmed.ncbi.nlm.nih.gov/14684687/) |  |
| 2 | 10158 | m.10158T\>C | T10158C\-F2 | France | Leigh encephalopathy, failure to thrive, high plasma/urinary lactate, MRI putamen lesion | 0 | 0 | 2003 | [14684687](https://pubmed.ncbi.nlm.nih.gov/14684687/) |  |
| 3 | 10158 | m.10158T\>C | T10158C\-F3 | Australia | Leigh disease, dystonia | 0 | 0 | 2004 | [14705112](https://pubmed.ncbi.nlm.nih.gov/14705112/) | Carring T10191C |
| 4 | 10158 | m.10158T\>C | T10158C\-F4 | Australia | Leigh\-like/lethal infantile mitochondrial disease, seizures, failure to thrive, hepatomegaly, hypotonia, high blood/CSF lactate, brain white matter/brainstem lesions | 0 | 0 | 2004 | [14705112](https://pubmed.ncbi.nlm.nih.gov/14705112/) | Carring T10191C |
| 5 | 10158 | m.10158T\>C | [T10158C\-F5 ](https://mitofam.com/doc/1213/)| Australia | Lethal infantile mitochondrial disease, neonatal coma, hypothermia, metabolic acidosis, elevated blood/CSF lactate Unaffected mother | 1 | 0 | 2004 | [14705112](https://pubmed.ncbi.nlm.nih.gov/14705112/) | Carring T10191C |
| 6 | 10158 | m.10158T\>C | T10158C\-F6 | Greece | Leigh syndrome | 0 | 0 | 2004 | [14764913](https://pubmed.ncbi.nlm.nih.gov/14764913/) |  |
| 7 | 10158 | m.10158T\>C | T10158C\-F7 | Italy | Leigh syndrome | ND | ND | 2004 | [15576045](https://pubmed.ncbi.nlm.nih.gov/15576045/) |  |
| 8 | 10158 | m.10158T\>C | T10158C\-F8 | United States | Leigh syndrome | ND | ND | 2011 | [22115768](https://pubmed.ncbi.nlm.nih.gov/22115768/) |  |
| 9 | 10158 | m.10158T\>C |[ T10158C\-F9 ](https://mitofam.com/doc/1214/)| United Kingdom | Undetermined mitochondrial diseases | ND | ND | 2007 | [24642831](https://pubmed.ncbi.nlm.nih.gov/24642831/) |  |
| 10 | 10158 | m.10158T\>C |[ T10158C\-F10](https://mitofam.com/doc/1215/) | Italy | MELAS, stroke\-like episodes | 1 | 0 | 2013 | [27742419](https://pubmed.ncbi.nlm.nih.gov/27742419/) |  |
| 11 | 10158 | m.10158T\>C | T10158C\-F11 | Japan | MELAS, stroke\-like episodes | ND | ND | 2017 | [28050007](https://pubmed.ncbi.nlm.nih.gov/28050007/) |  |
| 12 | 10158 | m.10158T\>C | T10158C\-F12 | Japan | Leigh syndrome | ND | ND | 2016 | [28429146](https://pubmed.ncbi.nlm.nih.gov/28429146/) |  |
| 13 | 10158 | m.10158T\>C | T10158C\-F13 | Japan | Leigh syndrome | ND | ND | 2016 | [28429146](https://pubmed.ncbi.nlm.nih.gov/28429146/) |  |
| 14 | 10158 | m.10158T\>C | T10158C\-F14 | Japan | Leigh encephalopathy, scarce eye movement, diminished muscle tone, elevated blood/CSF lactate, MRI lesions, convulsions, alive at 5 years | 0 | 0 | 2017 | [28916229](https://pubmed.ncbi.nlm.nih.gov/28916229/) |  |
| 15 | 10158 | m.10158T\>C | T10158C\-F15 | Japan | Stroke\-like episodes | ND | ND | 2017 | [29237403](https://pubmed.ncbi.nlm.nih.gov/29237403/) |  |
| 16 | 10158 | m.10158T\>C | T10158C\-F16 | China | Stroke\-like episodes | ND | ND | 2018 | [30128709](https://pubmed.ncbi.nlm.nih.gov/30128709/) |  |
| 17 | 10158 | m.10158T\>C | T10158C\-F17 | Czech Republic | MELAS | ND | ND | 2020 | [31996177](https://pubmed.ncbi.nlm.nih.gov/31996177/) |  |
| 18 | 10158 | m.10158T\>C | T10158C\-F18 | Italy | Leigh syndrome, MELAS | ND | ND | 2019 | [32504279](https://pubmed.ncbi.nlm.nih.gov/32504279/) |  |
| 19 | 10158 | m.10158T\>C | T10158C\-F19 | United Kingdom | Undetermined mitochondrial diseases | 0 | 0 | 2021 | [34732400](https://pubmed.ncbi.nlm.nih.gov/34732400/) |  |
| 20 | 10158 | m.10158T\>C | T10158C\-F20 | China | MELAS, stroke\-like episodes | ND | ND | 2015 | [41623499](https://pubmed.ncbi.nlm.nih.gov/41623499/) |  |

# **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 | 10158 | m.10158T\>C | T10158C\-F1 | T10158C\-F1\-P1 | De novo | F | Y | Y | D | 5 mo | 0 | 85% | / | / | Leigh disease, poor visual contact, floppiness, abnormal movements |  |
| 2 | 10158 | m.10158T\>C | T10158C\-F2 | T10158C\-F2\-P1 | De novo | M | Y | Y | D | 7 mo | 0 | 85% | / | / | Leigh encephalopathy, failure to thrive |  |
| 3 | 10158 | m.10158T\>C | T10158C\-F3 | T10158C\-F3\-P1 | De novo | F | Y | Y | D | 3 y 9 mo | / | 91% | / | 81%(F); 87%(Lymphoblasts) | Leigh disease, poor weight gain, delayed motor development, dystonia, seizures, bulbar palsy | Carring T10191C |
| 4 | 10158 | m.10158T\>C | T10158C\-F4 | T10158C\-F4\-P1 | De novo | F | Y | Y | D | 6 mo | / | 97% | / | 95%(F) | Leigh\-like/lethal infantile mitochondrial disease, seizures, failure to thrive, hepatomegaly, hypotonia | Carring T10191C |
| 5 | 10158 | m.10158T\>C | T10158C\-F5 | T10158C\-F5\-Ⅰ1 | Uninf | F | N | N | A | ND | / | / | / | 7%(F) | Healthy | Carring T10191C |
| 6 | 10158 | m.10158T\>C | T10158C\-F5 | T10158C\-F5\-Ⅱ1 | Fam | M | Y | Y | D | 22 d | / | / | / | \>98%(Other tissue) | Lethal infantile mitochondrial disease, neonatal coma, hypothermia | Carring T10191C |
| 7 | 10158 | m.10158T\>C | T10158C\-F6 | T10158C\-F6\-P1 | De novo | M | Y | Y | D | 9 mo | 48% | 83% | / | / | Severe Leigh syndrome, hypotonia, nystagmus, no eye contact |  |
| 8 | 10158 | m.10158T\>C | T10158C\-F7 | T10158C\-F7\-P1 | Uninf | ND | Y | Y | ND | ND | / | / | / | Homo(F) | Leigh syndrome |  |
| 9 | 10158 | m.10158T\>C | T10158C\-F8 | T10158C\-F8\-P1 | Uninf | M | Y | Y | A | 6 y | 65% | / | / | / | Leigh syndrome, seizures and stroke\-like episode during course |  |
| 10 | 10158 | m.10158T\>C | T10158C\-F9 | T10158C\-F9\-Ⅰ1 | Fam | F | Y | ND | A | ND | 5% | / | 33% | 16%(BM) | Undetermined mitochondrial diseases |  |
| 11 | 10158 | m.10158T\>C | T10158C\-F9 | T10158C\-F9\-Ⅱ1 | Fam | ND | N | ND | ND | prenatal | / | / | / | 52%(Chorionic villus) | Healthy |  |
| 12 | 10158 | m.10158T\>C | T10158C\-F10 | T10158C\-F10\-Ⅰ1 | Uninf | F | N | N | A | ND | 10% | / | 70% | 50%(BM) | Healthy |  |
| 13 | 10158 | m.10158T\>C | T10158C\-F10 | T10158C\-F10\-Ⅱ1 | Fam | M | Y | Y | A | 11 y | 70% | 95% | 95% | 80%(BM) | MELAS\-like phenotype, epilepsia partialis continua, stroke\-like episodes/headache/vomiting |  |
| 14 | 10158 | m.10158T\>C | T10158C\-F11 | T10158C\-F11\-P1 | Uninf | M | Y | Y | A | 41 y | / | 69\.5% | / | / | Adult\-onset MELAS\-like encephalopathy, recurrent stroke\-like episodes, seizures, higher cerebral dysfunction, myoclonus, gait disturbance, dysarthria |  |
| 15 | 10158 | m.10158T\>C | T10158C\-F12 | T10158C\-F12\-P1 | Uninf | ND | Y | Y | ND | ND | 80% | / | / | / | Leigh syndrome |  |
| 16 | 10158 | m.10158T\>C | T10158C\-F13 | T10158C\-F13\-P1 | Uninf | ND | Y | Y | ND | ND | 100% | / | / | / | Leigh syndrome |  |
| 17 | 10158 | m.10158T\>C | T10158C\-F14 | T10158C\-F14\-P1 | De novo | F | Y | Y | A | 6 mo | 90% | / | / | / | Leigh encephalopathy, scarce eye movement, diminished muscle tone, convulsions |  |
| 18 | 10158 | m.10158T\>C | T10158C\-F15 | T10158C\-F15\-P1 | Uninf | M | Y | Y | A | 55 y | / | 76% | / | / | Repeated stroke\-like episodes, recurrent epilepsy, severe cognitive impairment |  |
| 19 | 10158 | m.10158T\>C | T10158C\-F16 | T10158C\-F16\-P1 | Uninf | F | Y | Y | ND | 12 y | 15% | / | / | / | Mental retardation, seizures, stroke\-like episodes, ataxia, pyramidal signs, bulbar palsy |  |
| 20 | 10158 | m.10158T\>C | T10158C\-F17 | T10158C\-F17\-P1 | Uninf | ND | Y | Y | A | 31 y | / | 53% | / | / | MELAS syndrome, stroke\-like episode, epilepsy, migraine, visual impairment, hearing loss, mental insufficiency/psychiatric disturbance |  |
| 21 | 10158 | m.10158T\>C | T10158C\-F18 | T10158C\-F18\-P1 | Uninf | M | Y | Y | ND | 15 y | / | / | / | \+ | MELAS/Leigh syndrome |  |
| 22 | 10158 | m.10158T\>C | T10158C\-F19 | T10158C\-F19\-P1 | De novo | F | Y | Y | ND | 26 y | / | / | / | 23%(Other tissue) | Undetermined mitochondrial diseases |  |
| 23 | 10158 | m.10158T\>C | T10158C\-F20 | T10158C\-F20\-P1 | Uninf | F | Y | Y | A | 52 y | / | 67% | / | / | MELAS, recurrent stroke\-like episodes, seizures, right lower limb weakness, dysarthria, mild cognitive impairment |  |

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