T8993G

# General Information

| **Position** | **8993** | **Variant** | **m.8993T\>G** | **Locus** | **MT\-ATP6** | **Amino\-AcidChange** | **L156R** |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Homoplasmy** | \+ | **Heteroplasmy** | \+ | **APOGEE2** | 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.8993T\>G** variant in MT\-ATP6 has been reported in 53 pedigrees. To date, 167 carriers have been reported. Homoplasmy was reported in 1/167 carriers (0\.6%), and 104/167 carriers (62\.3%) were affected. In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in fibroblasts (39%) than in heart (18%). In one affected carrier, a marked tissue\-specific difference was observed, with higher mutation loads in muscle (60%) and fibroblasts (80%) than in blood (30%). Similar tissue\-specific differences were observed in 1 additional carriers. The main clinical manifestations among affected carriers included leigh syndrome, hypotonia, seizures, ataxia, developmental delay, retinitis pigmentosa, peripheral neuropathy, leigh disease, and other features.

| **No.** | **Position** | **Variant** | **Family ID** | **Nationality** | **Diseases** | **Unaffected Maternal Relatives** | **Affected Maternal Relatives** | **Publication Year** | **PMID/Ref** | **Note** |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 1 | 8993 | m.8993T\>G | [T8993G\-F1](https://mitofam.com/doc/1696/) | United Kingdom | NARP; Leigh encephalopathy; developmental delay; retinitis pigmentosa | 6 | 6 | 1994 | [7529982](https://pubmed.ncbi.nlm.nih.gov/7529982/) |  |
| 2 | 8993 | m.8993T\>G |[ T8993G\-F2](https://mitofam.com/doc/1697/) | Finland | NARP syndrome; Leigh syndrome; retinitis pigmentosa; cognitive impairment; ataxia | 7 | 10 | 1995 | [7603783](https://pubmed.ncbi.nlm.nih.gov/7603783/) |  |
| 3 | 8993 | m.8993T\>G | [T8993G\-F3](https://mitofam.com/doc/1698/) | Czech Republic | Infantile lactate acidosis and encephalomyopathy | 1 | 3 | 1995 | [7605802](https://pubmed.ncbi.nlm.nih.gov/7605802/) |  |
| 4 | 8993 | m.8993T\>G | [T8993G\-F4](https://mitofam.com/doc/1699/) | Chinese | Leigh syndrome; hypertrophic cardiomyopathy | 1 | 2 | 1994 | [8042671](https://pubmed.ncbi.nlm.nih.gov/8042671/) | Stillborn sister and older sibling with sudden infant death had no molecular testing in this paper. |
| 5 | 8993 | m.8993T\>G | [T8993G\-F5](https://mitofam.com/doc/1700/) | United States | NARP; retinitis pigmentosa; neurologic manifestations; Leigh disease | 0 | 7 | 1993 | [8240109](https://pubmed.ncbi.nlm.nih.gov/8240109/) | Pedigree A |
| 6 | 8993 | m.8993T\>G | [T8993G\-F6](https://mitofam.com/doc/1701) | United States | NARP; retinitis pigmentosa; neurologic manifestations; Leigh disease | 0 | 4 | 1993 | [8240109](https://pubmed.ncbi.nlm.nih.gov/8240109/) | Pedigree B |
| 7 | 8993 | m.8993T\>G | [T8993G\-F7](https://mitofam.com/doc/1702) | United States | Leigh syndrome | 3 | 1 | 1993 | [8250532](https://pubmed.ncbi.nlm.nih.gov/8250532/) | case \#1 |
| 8 | 8993 | m.8993T\>G | [T8993G\-F8](https://mitofam.com/doc/1703) | United States | Leigh syndrome | 1 | 2 | 1993 | [8250532](https://pubmed.ncbi.nlm.nih.gov/8250532/) | case \#2 |
| 9 | 8993 | m.8993T\>G | T8993G\-F9 | United States | Leigh syndrome | 0 | 1 | 1993 | [8250532](https://pubmed.ncbi.nlm.nih.gov/8250532/) | case \#3 |
| 10 | 8993 | m.8993T\>G | [T8993G\-F10](https://mitofam.com/doc/1704) | United States | Leigh syndrome | 2 | 2 | 1993 | [8250532](https://pubmed.ncbi.nlm.nih.gov/8250532/) | case \#4,case \#5 |
| 11 | 8993 | m.8993T\>G | T8993G\-F11 | United States | Leigh syndrome | ND | ND | 1993 | [8250532](https://pubmed.ncbi.nlm.nih.gov/8250532/) | case \#6 |
| 12 | 8993 | m.8993T\>G | [T8993G\-F12](https://mitofam.com/doc/1705) | United States | Leigh syndrome | 1 | 0 | 1993 | [8250532](https://pubmed.ncbi.nlm.nih.gov/8250532/) | case \#7 |
| 13 | 8993 | m.8993T\>G | T8993G\-F13 | United States | Leigh syndrome | 1 | 1 | 1993 | [8250532](https://pubmed.ncbi.nlm.nih.gov/8250532/) | case \#8 |
| 14 | 8993 | m.8993T\>G | [T8993G\-F14 ](https://mitofam.com/doc/1706)| United States | Leigh syndrome | 2 | 0 | 1993 | [8250532](https://pubmed.ncbi.nlm.nih.gov/8250532/) | case \#9 |
| 15 | 8993 | m.8993T\>G | [T8993G\-F15](https://mitofam.com/doc/1707) | United States | Leigh syndrome | 1 | 1 | 1993 | [8250532](https://pubmed.ncbi.nlm.nih.gov/8250532/) | case \#10,case \#11 |
| 16 | 8993 | m.8993T\>G | T8993G\-F16 | United States | Leigh syndrome | 0 | 0 | 1993 | [8250532](https://pubmed.ncbi.nlm.nih.gov/8250532/) | case \#12 |
| 17 | 8993 | m.8993T\>G | [T8993G\-F23](https://mitofam.com/doc/1708/) | France | Maternally inherited Leigh syndrome; NARP syndrome | 5 | 3 | 1995 | [8750605](https://pubmed.ncbi.nlm.nih.gov/8750605/) |  |
| 18 | 8993 | m.8993T\>G | T8993G\-F24 | United States | NARP; syndromic retinitis pigmentosa | ND | ND | 1997 | [9222207](https://pubmed.ncbi.nlm.nih.gov/9222207/) |  |
| 19 | 8993 | m.8993T\>G | T8993G\-F25 | United States | NARP; syndromic retinitis pigmentosa | ND | ND | 1997 | [9222207](https://pubmed.ncbi.nlm.nih.gov/9222207/) |  |
| 20 | 8993 | m.8993T\>G | [T8993G\-F26](https://mitofam.com/doc/1709/) | France | Leigh syndrome; prenatal diagnosis | 5 | 1 | 1997 | [9329425](https://pubmed.ncbi.nlm.nih.gov/9329425/) |  |
| 21 | 8993 | m.8993T\>G | T8993G\-F27 | Japan | Leigh syndrome | 0 | 1 | 1998 | [9556461](https://pubmed.ncbi.nlm.nih.gov/9556461/) |  |
| 22 | 8993 | m.8993T\>G | [T8993G\-F28 ](https://mitofam.com/doc/1710/)| Australia | NARP; Leigh syndrome; prenatal diagnosis | 6 | 0 | 1999 | [10590437](https://pubmed.ncbi.nlm.nih.gov/10590437/) |  |
| 23 | 8993 | m.8993T\>G | [T8993G\-F29](https://mitofam.com/doc/1711) | Australia | Leigh syndrome; Leigh\-like syndrome; prenatal diagnosis | 4 | 1 | 1999 | [10590437](https://pubmed.ncbi.nlm.nih.gov/10590437/) |  |
| 24 | 8993 | m.8993T\>G | [T8993G\-F30](https://mitofam.com/doc/1712) | Portuguese | Leigh syndrome | 2 | 0 | 2000 | [10669202](https://pubmed.ncbi.nlm.nih.gov/10669202/) | Family A |
| 25 | 8993 | m.8993T\>G | [T8993G\-F31](https://mitofam.com/doc/1713) | Portuguese | Leigh syndrome | 1 | 1 | 2000 | [10669202](https://pubmed.ncbi.nlm.nih.gov/10669202/) | Family B |
| 26 | 8993 | m.8993T\>G | [T8993G\-F32](https://mitofam.com/doc/1714) | Portuguese | Leigh syndrome | 1 | 0 | 2000 | [10669202](https://pubmed.ncbi.nlm.nih.gov/10669202/) | Family C |
| 27 | 8993 | m.8993T\>G | [T8993G\-F33](https://mitofam.com/doc/1715) | United States | Subacute necrotizing encephalopathy; NARP | 0 | 4 | 1992 | [1436530](https://pubmed.ncbi.nlm.nih.gov/1436530/) |  |
| 28 | 8993 | m.8993T\>G | [T8993G\-F34 ](https://mitofam.com/doc/1716)| French | Cone\-rod dystrophy; NARP; Leigh syndrome suspected in untested child | 0 | 3 | 2001 | [11730668](https://pubmed.ncbi.nlm.nih.gov/11730668/) |  |
| 29 | 8993 | m.8993T\>G | [T8993G\-F35 ](https://mitofam.com/doc/1717)| Italian | NARP syndrome | 0 | 0 | 2002 | [11843698](https://pubmed.ncbi.nlm.nih.gov/11843698/) | Secondary biochemical\-clinical paper; clinical descriptions previously reported. |
| 30 | 8993 | m.8993T\>G | [T8993G\-F36](https://mitofam.com/doc/1718) | Italian | Incomplete NARP; NARP syndrome | 0 | 1 | 2002 | [11843698](https://pubmed.ncbi.nlm.nih.gov/11843698/) | Secondary biochemical\-clinical paper; clinical descriptions previously reported. |
| 31 | 8993 | m.8993T\>G | T8993G\-F37 | Italian | NARP\-Leigh syndrome | 0 | 0 | 2002 | [11843698](https://pubmed.ncbi.nlm.nih.gov/11843698/) | De novo\-compatible family in this paper. |
| 32 | 8993 | m.8993T\>G | [T8993G\-F41 ](https://mitofam.com/doc/1719/)| Italian | NARP or MILS | 3 | 0 | 2006 | [16402916](https://pubmed.ncbi.nlm.nih.gov/16402916/) |  |
| 33 | 8993 | m.8993T\>G | [T8993G\-F42](https://mitofam.com/doc/1720/) | Spanish | NARP\-MILS; adult Leigh/NARP continuum | 3 | 4 | 2006 | [16525806](https://pubmed.ncbi.nlm.nih.gov/16525806/) |  |
| 34 | 8993 | m.8993T\>G | [T8993G\-F43 ](https://mitofam.com/doc/1721/)| USA | NARP; Leigh syndrome; oligosymptomatic carrier | 1 | 2 | 2006 | [16546428](https://pubmed.ncbi.nlm.nih.gov/16546428/) |  |
| 35 | 8993 | m.8993T\>G | [T8993G\-F44](https://mitofam.com/doc/1722/) | French | Progressive myoclonic epilepsy; NARP mitochondriopathy | 0 | 1 | 2007 | [17452590](https://pubmed.ncbi.nlm.nih.gov/17452590/) |  |
| 36 | 8993 | m.8993T\>G | [T8993G\-F45 ](https://mitofam.com/doc/1723)| French | NARP prenatal diagnosis/risk | 1 | 0 | 2007 | [17545557](https://pubmed.ncbi.nlm.nih.gov/17545557/) | Family 1 |
| 37 | 8993 | m.8993T\>G | [T8993G\-F46](https://mitofam.com/doc/1724) | French | NARP prenatal diagnosis/risk | 0 | 0 | 2007 | [17545557](https://pubmed.ncbi.nlm.nih.gov/17545557/) | Family 3 |
| 38 | 8993 | m.8993T\>G | [T8993G\-F47 ](https://mitofam.com/doc/1725)| French | NARP prenatal diagnosis/risk | 1 | 1 | 2007 | [17545557](https://pubmed.ncbi.nlm.nih.gov/17545557/) | Family 4 |
| 39 | 8993 | m.8993T\>G | [T8993G\-F48](https://mitofam.com/doc/1726) | French | NARP prenatal diagnosis/risk | 1 | 0 | 2007 | [17545557](https://pubmed.ncbi.nlm.nih.gov/17545557/) | Family 5 |
| 40 | 8993 | m.8993T\>G | [T8993G\-F49 ](https://mitofam.com/doc/1727)| French | NARP prenatal diagnosis/risk | 2 | 4 | 2007 | [17545557](https://pubmed.ncbi.nlm.nih.gov/17545557/) | Family 6 |
| 41 | 8993 | m.8993T\>G |[ T8993G\-F50](https://mitofam.com/doc/1728) | Tunisia | Leigh syndrome | 6 | 3 | 2009 | [19433277](https://pubmed.ncbi.nlm.nih.gov/19433277/) |  |
| 42 | 8993 | m.8993T\>G | T8993G\-F51 | Netherlands | Leigh syndrome; de novo MT\-ATP6 mutation | 0 | 0 | 2017 | [27450679](https://pubmed.ncbi.nlm.nih.gov/27450679/) | Article case 1 |
| 43 | 8993 | m.8993T\>G | T8993G\-F52 | Netherlands | mtDNA disease; de novo MT\-ATP6 mutation | 0 | 0 | 2017 | [27450679](https://pubmed.ncbi.nlm.nih.gov/27450679/) | Article case 4 |
| 44 | 8993 | m.8993T\>G | [T8993G\-F53](https://mitofam.com/doc/1729/) | USA | Leigh syndrome; mitochondrial replacement therapy | 1 | 0 | 2016 | [27919073](https://pubmed.ncbi.nlm.nih.gov/27919073/) |  |
| 45 | 8993 | m.8993T\>G | [T8993G\-F54](https://mitofam.com/doc/1730/) | USA | Leigh syndrome; mitochondrial replacement therapy | 2 | 0 | 2016 | [27919073](https://pubmed.ncbi.nlm.nih.gov/27919073/) |  |
| 46 | 8993 | m.8993T\>G | [T8993G\-F55](https://mitofam.com/doc/1731) | Mexico | Leigh syndrome; mitochondrial replacement therapy | 2 | 1 | 2017 | [28385334](https://pubmed.ncbi.nlm.nih.gov/28385334/) |  |
| 47 | 8993 | m.8993T\>G | T8993G\-F56 | France | NARP syndrome; focal segmental glomerulosclerosis; end\-stage renal disease | 0 | 0 | 2017 | [29224958](https://pubmed.ncbi.nlm.nih.gov/29224958/) |  |
| 48 | 8993 | m.8993T\>G | T8993G\-F57 | USA | Maternally inherited Leigh syndrome | 0 | 0 | 2018 | [29602698](https://pubmed.ncbi.nlm.nih.gov/29602698/) |  |
| 49 | 8993 | m.8993T\>G | [T8993G\-F58](https://mitofam.com/doc/1732) | Australia | Leigh syndrome; sudden infant death syndrome | 1 | 2 | 1997 | [9199572](https://pubmed.ncbi.nlm.nih.gov/9199572/) |  |
| 50 | 8993 | m.8993T\>G | T8993G\-F59 | UK | Leigh syndrome; hearing loss | ND | ND | 2000 | [10611123](https://pubmed.ncbi.nlm.nih.gov/10611123/) |  |
| 51 | 8993 | m.8993T\>G | T8993G\-F60 | Japan | Leigh disease; lactic acidosis | ND | ND | 2006 | [16337222](https://pubmed.ncbi.nlm.nih.gov/16337222/) |  |
| 52 | 8993 | m.8993T\>G | T8993G\-F61 | Japan | Leigh disease; lactic acidosis | ND | ND | 2006 | [16337222](https://pubmed.ncbi.nlm.nih.gov/16337222/) |  |
| 53 | 8993 | m.8993T\>G | T8993G\-F62 | Serbia | Leigh syndrome | ND | ND | 2021 | [34829316](https://pubmed.ncbi.nlm.nih.gov/34829316/) |  |

# 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 | 8993 | m.8993T\>G | T8993G\-F1 | T8993G\-F1\-II2 | Fam | F | N | Y | A | 39 | 78% | / | / | / | Retinitis pigmentosa; mild sensory axonal neuropathy |  |
| 2 | 8993 | m.8993T\>G | T8993G\-F1 | T8993G\-F1\-III2 | Fam | M | N | Y | A | 14 | 88% | / | / | / | Learning difficulties; poor coordination; dysarthria; early peripheral retinal pigmentation |  |
| 3 | 8993 | m.8993T\>G | T8993G\-F1 | T8993G\-F1\-III4 | Fam | M | N | Y | A | 9 | 86% | / | / | / | Developmental delay; hypotonia; drowsiness; falls; speech delay; spastic\-ataxic dysarthria |  |
| 4 | 8993 | m.8993T\>G | T8993G\-F1 | T8993G\-F1\-III5 | Fam | M | N | Y | A | 11 | 87% | / | / | / | Mild clumsiness; slow immature speech |  |
| 5 | 8993 | m.8993T\>G | T8993G\-F1 | T8993G\-F1\-III6 | Fam | F | N | Y | A | 6 | 93% | / | / | / | Infantile hypotonia; delayed motor skills; poor vision; speech delay; dysarthria |  |
| 6 | 8993 | m.8993T\>G | T8993G\-F1 | T8993G\-F1\-III7 | Fam | F | N | Y | A | 4\.5 | 93% | / | / | / | Hypotonia; episodic drowsiness; speech delay; mild metabolic acidosis |  |
| 7 | 8993 | m.8993T\>G | T8993G\-F2 | T8993G\-F2\-I2 | Uninf | F | N | Y | A | ND | 36% | / | / | / | Migraine |  |
| 8 | 8993 | m.8993T\>G | T8993G\-F2 | T8993G\-F2\-II8 | Fam | F | N | Y | A | ND | 36% | / | / | / | Migraine |  |
| 9 | 8993 | m.8993T\>G | T8993G\-F2 | T8993G\-F2\-II9 | Fam | M | N | Y | A | 50 | 68% | / | / | / | Cognitive impairment; retinitis pigmentosa; visual handicap; migraine |  |
| 10 | 8993 | m.8993T\>G | T8993G\-F2 | T8993G\-F2\-III1 | Fam | F | N | Y | A | 37 | 54% | 60% | / | / | Mild visual adaptation impairment |  |
| 11 | 8993 | m.8993T\>G | T8993G\-F2 | T8993G\-F2\-III2 | Fam | F | N | Y | A | 34 | 78% | / | / | / | Cognitive impairment; sensorineural hearing deficit; retinitis pigmentosa |  |
| 12 | 8993 | m.8993T\>G | T8993G\-F2 | T8993G\-F2\-III6 | Fam | M | N | Y | A | 20 | 80% | 85% | / | / | Infantile spasms; ataxia; vomiting; retinitis pigmentosa; mental retardation |  |
| 13 | 8993 | m.8993T\>G | T8993G\-F2 | T8993G\-F2\-III8 | Fam | M | N | N | A | ND | 40% | / | / | / | Healthy |  |
| 14 | 8993 | m.8993T\>G | T8993G\-F2 | T8993G\-F2\-III9 | Fam | F | N | N | A | ND | 44% | / | / | / | Healthy |  |
| 15 | 8993 | m.8993T\>G | T8993G\-F2 | T8993G\-F2\-IV1 | Fam | F | N | N | A | ND | 41% | / | / | / | Healthy |  |
| 16 | 8993 | m.8993T\>G | T8993G\-F2 | T8993G\-F2\-IV2 | Fam | M | N | Y | D | 2 | / | 92% | / | / | Severe infantile encephalomyopathy; optic atrophy; retinal degeneration |  |
| 17 | 8993 | m.8993T\>G | T8993G\-F2 | T8993G\-F2\-IV3 | Fam | F | N | Y | D | 7mo | / | 98% | / | 96%(BRAIN); 91%(Heart); 86%(Liver); 97%(KIDNEY) | Leigh syndrome |  |
| 18 | 8993 | m.8993T\>G | T8993G\-F3 | T8993G\-F3\-I1 | Uninf | F | N | N | A | ND | 50% | / | / | 50%(F) | Healthy |  |
| 19 | 8993 | m.8993T\>G | T8993G\-F3 | T8993G\-F3\-II2 | Fam | M | N | Y | A | 3mo | \>99% | / | / | \>99%(F) | Hypotonia; seizures; apneic spells; psychomotor retardation; lactic acidosis |  |
| 20 | 8993 | m.8993T\>G | T8993G\-F3 | T8993G\-F3\-II3 | Fam | M | N | Y | D | 3\.5mo | \>99% | / | / | \>99%(F) | Infantile lactate acidosis and encephalomyopathy |  |
| 21 | 8993 | m.8993T\>G | T8993G\-F3 | T8993G\-F3\-II4 | Fam | M | Y | Y | A | 8 | 96% | / | / | / | Infantile lactate acidosis and encephalomyopathy |  |
| 22 | 8993 | m.8993T\>G | T8993G\-F4 | T8993G\-F4\-III3 | Fam | M | Y | Y | D | 6mo | / | 90% | / | 84%(MYOBLASTCULTURE); 90%(F) | Leigh syndrome; hypertrophic cardiomyopathy; developmental delay; hypotonia; lactic acidosis |  |
| 23 | 8993 | m.8993T\>G | T8993G\-F4 | T8993G\-F4\-III2 | Fam | M | N | Y | D | 2mo | / |  |  |  | sudden infant death syndrome |  |
| 24 | 8993 | m.8993T\>G | T8993G\-F4 | T8993G\-F4\-III1 | Fam | F | N | Y | D | 0 | / |  |  |  | stillborn |  |
| 25 | 8993 | m.8993T\>G | T8993G\-F4 | T8993G\-F4\-II2 | Uninf | F | N | N | A | ND | 38% | / | / | / | Healthy |  |
| 26 | 8993 | m.8993T\>G | T8993G\-F5 | T8993G\-F5\-II1 | Fam | M | N | Y | A | 44 | 99\.6% | / | / | / | Severe retinitis pigmentosa; dementia; seizures; deafness |  |
| 27 | 8993 | m.8993T\>G | T8993G\-F5 | T8993G\-F5\-II3 | Fam | F | N | Y | A | ND | \+ | / | / | / | Salt\-and\-pepper retinopathy; migraine |  |
| 28 | 8993 | m.8993T\>G | T8993G\-F5 | T8993G\-F5\-III2 | Fam | ND | N | Y | A | ND | \+ | / | / | / | Salt\-and\-pepper retinopathy; migraine |  |
| 29 | 8993 | m.8993T\>G | T8993G\-F5 | T8993G\-F5\-III4 | Fam | ND | N | Y | A | ND | \+ | / | / | / | Ocular migraine |  |
| 30 | 8993 | m.8993T\>G | T8993G\-F5 | T8993G\-F5\-III5 | Fam | ND | N | Y | A | ND | \+ | / | / | / | Migraine |  |
| 31 | 8993 | m.8993T\>G | T8993G\-F5 | T8993G\-F5\-IV2 | Fam | M | N | Y | A | 2\.5 | \+ | / | / | / | Poor motor coordination; delayed speech |  |
| 32 | 8993 | m.8993T\>G | T8993G\-F5 | T8993G\-F5\-IV3 | Fam | M | N | Y | A | 18mo | \+ | / | / | / | Leigh disease; chronic metabolic acidosis |  |
| 33 | 8993 | m.8993T\>G | T8993G\-F6 | T8993G\-F6\-I1 | Uninf | F | N | Y | A | 41 | \+ | / | / | / | Retinal pigmentary degeneration; migraine; fatigability |  |
| 34 | 8993 | m.8993T\>G | T8993G\-F6 | T8993G\-F6\-II1 | Fam | F | N | Y | D | 2\.5 | \+ | / | / | / | Leigh disease |  |
| 35 | 8993 | m.8993T\>G | T8993G\-F6 | T8993G\-F6\-II2 | Fam | M | N | Y | A | 14 | \+ | / | / | / | Developmental delay; ataxia; retinal vascular attenuation; rod\-cone dysfunction |  |
| 36 | 8993 | m.8993T\>G | T8993G\-F6 | T8993G\-F6\-II3 | Fam | M | N | Y | A | 12 | \+ | / | / | / | Developmental delay; dementia; ataxia |  |
| 37 | 8993 | m.8993T\>G | T8993G\-F6 | T8993G\-F6\-II4 | Fam | F | N | Y | D | 14mo | \+ | / | / | / | Leigh disease |  |
| 38 | 8993 | m.8993T\>G | T8993G\-F7 | T8993G\-F7\-I2 | Uninf | F | N | N | A | 23 | 53% | / | / | / | proximal weakness/depression noted |  |
| 39 | 8993 | m.8993T\>G | T8993G\-F7 | T8993G\-F7\-II3 | Fam | M | Y | Y | D | 3mo | / | 93% | / | 92%(F) | Leigh syndrome; developmental delay; hypotonia; seizures; peripheral neuropathy; cardiac/respiratory impairment |  |
| 40 | 8993 | m.8993T\>G | T8993G\-F8 | T8993G\-F8\-II2 | Fam | F | N | N | A | ND | 41% | / | / | / | Healthy |  |
| 41 | 8993 | m.8993T\>G | T8993G\-F8 | T8993G\-F8\-III3 | Fam | M | Y | Y | D | ND | / | 90% | / | 90%(F); 84%(MUSCLECULTURE) | Leigh syndrome; developmental delay; hypotonia; cardiac/respiratory impairment |  |
| 42 | 8993 | m.8993T\>G | T8993G\-F9 | T8993G\-F9\-II2 | Fam | M | Y | Y | D | 3mo | / | 94% | / | / | Leigh syndrome; developmental delay; hypotonia; ataxia; retinopathy; seizures |  |
| 43 | 8993 | m.8993T\>G | T8993G\-F10 | T8993G\-F10\-III1 | Fam | M | Y | Y | D | 2\.5mo | / | 95% | / | / | Leigh syndrome; developmental delay; hypotonia; ataxia; optic atrophy; pyramidal signs |  |
| 44 | 8993 | m.8993T\>G | T8993G\-F10 | T8993G\-F10\-III2 | Fam | M | Y | Y | D | 3mo | / | 94% | / | / | Leigh syndrome; developmental delay; hypotonia; optic atrophy |  |
| 45 | 8993 | m.8993T\>G | T8993G\-F11 | T8993G\-F11\-III1 | Uninf | M | Y | Y | D | 3mo | / | 94% | / | / | Leigh syndrome; developmental delay; hypotonia; seizures; peripheral neuropathy; cardiac/respiratory impairment |  |
| 46 | 8993 | m.8993T\>G | T8993G\-F12 | T8993G\-F12\-I2 | Uninf | F | N | N | A | ND | 56% | / | / | / | Healthy |  |
| 47 | 8993 | m.8993T\>G | T8993G\-F12 | T8993G\-F12\-II1 | Fam | M | Y | Y | ND | 3mo | 88% | 90% | / | 90%(F) | Leigh syndrome; developmental delay; hypotonia; peripheral neuropathy; pyramidal signs |  |
| 48 | 8993 | m.8993T\>G | T8993G\-F13 | T8993G\-F13\-II2 | Fam | M | Y | Y | A | ND | / | 84% | / | / | Leigh syndrome; developmental delay; hypotonia; ataxia; retinopathy; ophthalmoparesis; seizures |  |
| 49 | 8993 | m.8993T\>G | T8993G\-F14 | T8993G\-F14\-II2 | Uninf | F | N | N | A | ND | 62% | / | / | / | Healthy |  |
| 50 | 8993 | m.8993T\>G | T8993G\-F14 | T8993G\-F14\-III1 | Fam | M | N | N | A | ND | 79% | / | / | / | Healthy |  |
| 51 | 8993 | m.8993T\>G | T8993G\-F14 | T8993G\-F14\-III2 | Fam | M | N | N | A | ND | 77% | / | / | / | Healthy |  |
| 52 | 8993 | m.8993T\>G | T8993G\-F14 | T8993G\-F14\-III3 | Fam | F | Y | Y | D | 5mo | / | 90% | / | / | Leigh syndrome; developmental delay; hypotonia; ataxia; seizures; respiratory impairment |  |
| 53 | 8993 | m.8993T\>G | T8993G\-F15 | T8993G\-F15\-I2 | Uninf | F | N | N | A | ND | 76% | / | / | / | Healthy |  |
| 54 | 8993 | m.8993T\>G | T8993G\-F15 | T8993G\-F15\-II2 | Fam | F | Y | Y | ND | 3mo | / | 95% | / | 95%(F); 95%(MUSCLECULTURE); 95%(PERIPHERALNERVE); 95%(BRAIN) | Leigh syndrome; developmental delay; hypotonia; ophthalmoparesis; seizures; respiratory impairment |  |
| 55 | 8993 | m.8993T\>G | T8993G\-F15 | T8993G\-F15\-II1 | Fam | F | Y | Y | D | 6\.5mo | 90% | / | / | / | Leigh syndrome; developmental delay; hypotonia; ophthalmoparesis; seizures; respiratory impairment |  |
| 56 | 8993 | m.8993T\>G | T8993G\-F16 | T8993G\-F16\-II2 | Uninf | F | Y | Y | ND | 1mo | / | 94% | / | / | Leigh syndrome; developmental delay; hypotonia; respiratory impairment |  |
| 57 | 8993 | m.8993T\>G | T8993G\-F23 | T8993G\-F23\-I2 | Uninf | F | N | N | A | ND | 84% | / | / | 98%(F) | Healthy |  |
| 58 | 8993 | m.8993T\>G | T8993G\-F23 | T8993G\-F23\-II4 | Fam | F | N | Y | A | ND | 99% | / | / | / | Mental retardation; ataxia; dysarthria; dystonia; pes cavus; retinal degeneration; apneic episodes |  |
| 59 | 8993 | m.8993T\>G | T8993G\-F23 | T8993G\-F23\-II5 | Fam | F | N | N | A | ND | 63% | / | / | 80%(F) | Healthy |  |
| 60 | 8993 | m.8993T\>G | T8993G\-F23 | T8993G\-F23\-II6 | Fam | F | N | N | A | ND | 91% | / | / | 86%(F) | Healthy |  |
| 61 | 8993 | m.8993T\>G | T8993G\-F23 | T8993G\-F23\-II7 | Fam | F | Y | Y | D | 9 | / | 100% | / | / | Leigh syndrome; hypotonia; developmental delay; ataxia; myopathic weakness; retinitis; deafness; seizures |  |
| 62 | 8993 | m.8993T\>G | T8993G\-F23 | T8993G\-F23\-II8 | Fam | M | N | N | A | ND | 45% | / | / | 65%(F) | Healthy |  |
| 63 | 8993 | m.8993T\>G | T8993G\-F23 | T8993G\-F23\-II10 | Fam | M | N | N | A | ND | 98% | / | / | 98%(F) | Healthy |  |
| 64 | 8993 | m.8993T\>G | T8993G\-F24 | T8993G\-F24\-P1 | De novo | M | Y | Y | A | 38 | 72% | 75% | / | / | NARP; retinitis pigmentosa; hearing loss; sensorimotor axonal polyneuropathy; mild mental retardation | Mother muscle/blood and brother blood negative. |
| 65 | 8993 | m.8993T\>G | T8993G\-F25 | T8993G\-F25\-P2 | Uninf | F | Y | Y | D | 39 | / | 85% | / | / | NARP; retinitis pigmentosa; ataxia; seizures; ophthalmoparesis; heart conduction block |  |
| 66 | 8993 | m.8993T\>G | T8993G\-F26 | T8993G\-F26\-I1 | Uninf | F | N | N | A | ND | 10% | / | / | / | Healthy |  |
| 67 | 8993 | m.8993T\>G | T8993G\-F26 | T8993G\-F26\-II1 | Fam | F | N | N | A | 25 | 50% | / | / | / | Healthy |  |
| 68 | 8993 | m.8993T\>G | T8993G\-F26 | T8993G\-F26\-II2 | Fam | F | N | N | A | 24 | 52% | / | / | 84%(F) | Healthy |  |
| 69 | 8993 | m.8993T\>G | T8993G\-F26 | T8993G\-F26\-II4 | Fam | M | N | N | A | ND | 0 |  |  |  | Healthy |  |
| 70 | 8993 | m.8993T\>G | T8993G\-F26 | T8993G\-F26\-II5 | Fam | F | N | N | A | 14 | 0 |  |  |  | Healthy |  |
| 71 | 8993 | m.8993T\>G | T8993G\-F26 | T8993G\-F26\-III2 | Fam | F | Y | Y | D | 14mo | / | / | / | 90%(F) | Leigh syndrome; seizures; hypotonia; dysphagia; lactic acidosis |  |
| 72 | 8993 | m.8993T\>G | T8993G\-F26 | T8993G\-F26\-III1 | Fam | F | N | ND | D | fetus | / | / | / | 96%(CVS); 91%(BONE); 94%(BRAIN); 93%(GASTROINTESTINALTRACT); 95%(Heart); 95%(KIDNEY); 96%(LUNG); 95%(Muscle); 94%(SPINALCORD) | No postnatal phenotype | Pregnancy medically interrupted. |
| 73 | 8993 | m.8993T\>G | T8993G\-F27 | T8993G\-F27\-III2 | De novo | M | Y | Y | A | 1 | \>95% | \>95% | \>95% | \>95%(F) | Leigh syndrome; generalized hypotonia; apnea attacks; altered consciousness; lactic acidosis |  |
| 74 | 8993 | m.8993T\>G | T8993G\-F28 | T8993G\-F28\-I2 | Uninf | F | N | N | A | ND | 11% | / | / | / | Healthy |  |
| 75 | 8993 | m.8993T\>G | T8993G\-F28 | T8993G\-F28\-II1 | Fam | M | Y | Y | A | ND | 79% | / | / | 92%(F) | NARP |  |
| 76 | 8993 | m.8993T\>G | T8993G\-F28 | T8993G\-F28\-II2 | Fam | F | N | N | A | ND | 59% | / | / | / | Healthy |  |
| 77 | 8993 | m.8993T\>G | T8993G\-F28 | T8993G\-F28\-II3 | Fam | F | N | N | A | ND | 7% | / | / | / | Healthy |  |
| 78 | 8993 | m.8993T\>G | T8993G\-F28 | T8993G\-F28\-II5 | Fam | F | N | N | A | ND | 5% | / | / | / | Healthy |  |
| 79 | 8993 | m.8993T\>G | T8993G\-F29 | T8993G\-F29\-I2 | Uninf | F | N | N | A | ND | 53% | / | / | / | Healthy |  |
| 80 | 8993 | m.8993T\>G | T8993G\-F29 | T8993G\-F29\-II3 | Fam | M | Y | Y | D | ND | / | 93% | / | 92%(F) | Leigh syndrome |  |
| 81 | 8993 | m.8993T\>G | T8993G\-F30 | T8993G\-F30\-III1 | Fam | M | Y | Y | A | 3 y | / | 95% | / | / | Leigh syndrome; hypotonia, psychomotor regression, myoclonic seizures, basal ganglia lesions |  |
| 82 | 8993 | m.8993T\>G | T8993G\-F30 | T8993G\-F30\-II3 | De novo | F | N | N | A | ND | 21% | / | / | / | Healthy |  |
| 83 | 8993 | m.8993T\>G | T8993G\-F30 | T8993G\-F30\-III2 | Fam | F | N | N | A | ND | 49% | / | / | / | Healthy |  |
| 84 | 8993 | m.8993T\>G | T8993G\-F31 | T8993G\-F31\-II1 | Fam | F | Y | Y | A | 2 y onset | \>99% | \>99% | / | / | Leigh syndrome; dystonia, choreic movements, basal ganglia lesions |  |
| 85 | 8993 | m.8993T\>G | T8993G\-F31 | T8993G\-F31\-I2 | Uninf | F | N | N | A | ND | 76% | / | / | / | Healthy |  |
| 86 | 8993 | m.8993T\>G | T8993G\-F31 | T8993G\-F31\-II2 | Fam | F | N | Y | A | 8 y | \>99% | / | / | / | Mental retardation, spastic paraparesis, elevated lactate |  |
| 87 | 8993 | m.8993T\>G | T8993G\-F32 | T8993G\-F32\-III3 | Fam | F | Y | Y | A | 7 y | / | 95% | / | / | Leigh syndrome; psychomotor regression, seizures, hypotonia, brain atrophy and basal ganglia lesions |  |
| 88 | 8993 | m.8993T\>G | T8993G\-F32 | T8993G\-F32\-II4 | Uninf | F | N | N | A | ND | \<5% | / | / | / | Healthy |  |
| 89 | 8993 | m.8993T\>G | T8993G\-F33 | T8993G\-F33\-II1 | Uninf | F | N | Y | A | ND | 86% | / | / | / | Pigmentary retinopathy, impaired night vision, migraine headaches |  |
| 90 | 8993 | m.8993T\>G | T8993G\-F33 | T8993G\-F33\-III1 | Fam | F | N | Y | D | 2\.5 y | / | / | / | 82%(BRAIN) | SNE/Leigh disease; severe psychomotor retardation, hypotonia, seizures, respiratory arrest |  |
| 91 | 8993 | m.8993T\>G | T8993G\-F33 | T8993G\-F33\-III2 | Fam | M | N | Y | A | 11 y | \>95% | 92% | / | / | Moderate psychomotor retardation, pigmentary retinopathy, episodic ataxia |  |
| 92 | 8993 | m.8993T\>G | T8993G\-F33 | T8993G\-F33\-III3 | Fam | M | N | Y | A | 14 y | \>95% | 95% | / | / | Moderate psychomotor retardation, pigmentary retinopathy, episodic ataxia |  |
| 93 | 8993 | m.8993T\>G | T8993G\-F33 | T8993G\-F33\-III4 | Fam | F | N | Y | D | 14 mo | / | / | / | 77%(BRAIN) | SNE/Leigh disease; severe psychomotor retardation, hypotonia, dystonia, apnea |  |
| 94 | 8993 | m.8993T\>G | T8993G\-F34 | T8993G\-F34\-I2 | Uninf | F | Y | Y | A | 42 | 50% | / | / | / | Late\-onset cone\-rod dystrophy; mild NARP symptoms |  |
| 95 | 8993 | m.8993T\>G | T8993G\-F34 | T8993G\-F34\-II1 | Fam | M | N | Y | A | 22 | 75% | / | / | / | Marked NARP symptoms; psychomotor retardation, ataxia, seizures, proximal muscle weakness, retinal dystrophy |  |
| 96 | 8993 | m.8993T\>G | T8993G\-F34 | T8993G\-F34\-II2 | Fam | M | N | Y | A | 21 | 75% | / | / | / | Marked NARP symptoms; mild mental retardation, delayed speech, mild ataxia, advanced retinal dystrophy |  |
| 97 | 8993 | m.8993T\>G | T8993G\-F34 | T8993G\-F34\-II3 | Fam | M | N | Y | D | 4 y | / | / | / | / | Seizures from 7 mo; regression; hypotonia; brainstem dysfunction; bull's\-eye retinal dystrophy; basal ganglia/brainstem lesions; elevated lactate/pyruvate; suspected Leigh disease |  |
| 98 | 8993 | m.8993T\>G | T8993G\-F35 | T8993G\-F35\-I1 | Uninf | F | N | Y | A | ND | 19% | / | / | 29%(U); 18%(Heart); 39%(F) | Muscle fatigue, headache, memory loss, paresthesias |  |
| 99 | 8993 | m.8993T\>G | T8993G\-F35 | T8993G\-F35\-II1 | Fam | F | Y | Y | A | 6 mo onset | 91% | / | 91% | 95%(Heart); 92%(F) | NARP syndrome; mental retardation, ataxia, dystonia, retinitis pigmentosa, optic atrophy, peripheral neuropathy, muscle atrophy |  |
| 100 | 8993 | m.8993T\>G | T8993G\-F35 | T8993G\-F35\-II2 | Fam | F | Y | Y | A | 1 y onset | 85% | / | 88% | 78%(Heart); 86%(F) | NARP syndrome; mental retardation, ataxia, seizures, retinitis pigmentosa, peripheral neuropathy, muscle atrophy |  |
| 101 | 8993 | m.8993T\>G | T8993G\-F36 | T8993G\-F36\-I1 | Uninf | F | Y | Y | A | 32 y onset | 55% | / | / |  | Incomplete NARP syndrome; retinitis pigmentosa, ataxia, periventricular white matter lesions |  |
| 102 | 8993 | m.8993T\>G | T8993G\-F36 | T8993G\-F36\-II1 | Fam | M | N | Y | A | 7 mo onset | 85% | / | / |  | NARP syndrome; mental retardation, ataxia, retinitis pigmentosa, peripheral neuropathy, muscle atrophy |  |
| 103 | 8993 | m.8993T\>G | T8993G\-F37 | T8993G\-F37\-II1 | De novo | M | Y | Y | A | 3 mo onset | 86% | 88% | 93% |  | NARP\-Leigh syndrome; mental retardation, recurrent coma, seizures, ataxia, retinitis pigmentosa, optic atrophy, peripheral neuropathy |  |
| 104 | 8993 | m.8993T\>G | T8993G\-F41 | T8993G\-F41\-I1 | Uninf | F | N | N | A | ND | 32% | / | / | / | Healthy |  |
| 105 | 8993 | m.8993T\>G | T8993G\-F41 | T8993G\-F41\-II1 | Fam | F | N | N | A | ND | 49% | / | / | / | Healthy |  |
| 106 | 8993 | m.8993T\>G | T8993G\-F41 | T8993G\-F41\-II2 | Fam | M | N | N | A | ND | 80% | / | / | / | Healthy |  |
| 107 | 8993 | m.8993T\>G | T8993G\-F41 | T8993G\-F41\-II3 | Fam | F | Y | Y | A | ND | 94% | / | / | / | NARP or MILS category |  |
| 108 | 8993 | m.8993T\>G | T8993G\-F42 | T8993G\-F42\-II3 | Fam | M | N | Y | A | 50 y onset | 53% | / | / | / | Retinitis pigmentosa, gait ataxia, psychosis |  |
| 109 | 8993 | m.8993T\>G | T8993G\-F42 | T8993G\-F42\-II4 | Fam | M | Y | Y | D | 64 y | 75% | 87% | / | 89%(brainstem/cortex); 90%(putamen/cerebellum); 91%(THALAMUS) | Retinitis pigmentosa, psychosis, deafness, ataxia, dystonia, chorea, pyramidalism, putaminal lesions |  |
| 110 | 8993 | m.8993T\>G | T8993G\-F42 | T8993G\-F42\-II5 | Fam | M | N | Y | A | 56 y onset | 69% | 77% | / | / | Retinitis pigmentosa, optic atrophy, deafness, dysarthria, mild gait ataxia, chorea, axonal polyneuropathy, seizures |  |
| 111 | 8993 | m.8993T\>G | T8993G\-F42 | T8993G\-F42\-II6 | Fam | F | N | N | A | 59 y | 0 | / | / | / | Healthy |  |
| 112 | 8993 | m.8993T\>G | T8993G\-F43 | T8993G\-F43\-II2 | Fam | F | N | N | A | 27 y | 41% | / | / | H 42/47%; 38%(BM); 40%(F) | No significant illness reported |  |
| 113 | 8993 | m.8993T\>G | T8993G\-F43 | T8993G\-F43\-III1 | Fam | F | N | Y | A | 6 y | 90% | / | / | H 60/73%; 94%(BM); 95%(F) | Oligosymptomatic; mild speech/articulation delay, normal motor development, regular school with resource help |  |
| 114 | 8993 | m.8993T\>G | T8993G\-F43 | T8993G\-F43\-III2 | Fam | M | Y | Y | A | 4 y | 90% | / | / | H 91/91%; 90%(BM); 92%(F) | NARP features; failure to thrive, hypotonia, developmental delay, ataxic gait, elevated lactate |  |
| 115 | 8993 | m.8993T\>G | T8993G\-F43 | T8993G\-F43\-III3 | Fam | M | N | Y | A | 2 y | 95% | / | / | H 95/97%; 95%(BM); 95%(F) | Leigh syndrome; hypotonia, regression, seizures, abnormal basal ganglia/brainstem MRI, lactic acidemia |  |
| 116 | 8993 | m.8993T\>G | T8993G\-F44 | T8993G\-F44\-I1 | Uninf | F | Y | Y | A | 46 y | 30% | 60% | / | 80%(F) | Progressive myoclonic epilepsy phenotype; myoclonus, epilepsy, ataxia, axonal sensorimotor polyneuropathy |  |
| 117 | 8993 | m.8993T\>G | T8993G\-F44 | T8993G\-F44\-II1 | Fam | F | N | Y | A | 25 y | 60% | / | / | / | Epilepsy since 17 y and ataxia since 18 y; normal psychomotor development |  |
| 118 | 8993 | m.8993T\>G | T8993G\-F45 | T8993G\-F45\-II2 | De novo | F | N | ND | A | ND | 17% | / | / | / | At\-risk pregnant carrier; clinical phenotype not reported |  |
| 119 | 8993 | m.8993T\>G | T8993G\-F45 | T8993G\-F45\-III4 | Fam | M | N | Y | D | ND | 1 | 1 | / | / | NARP |  |
| 120 | 8993 | m.8993T\>G | T8993G\-F45 | T8993G\-F45\-III5 | Fam | ND | N | N | A | 2 y follow\-up | 0 | / | / | AS2 0 | Healthy |  |
| 121 | 8993 | m.8993T\>G | T8993G\-F46 | T8993G\-F46\-I1 | Uninf | F | N | N | A | ND | 30% | / | / | / | Healthy |  |
| 122 | 8993 | m.8993T\>G | T8993G\-F46 | T8993G\-F46\-II3 | Fam | ND | N | ND | D | ND | / | / | / | 100%(CVS) | ND | Prenatal diagnosis paper. |
| 123 | 8993 | m.8993T\>G | T8993G\-F47 | T8993G\-F47\-I1 | Uninf | F | N | N | A | ND | 55% | / | / | / | Healthy |  |
| 124 | 8993 | m.8993T\>G | T8993G\-F47 | T8993G\-F47\-II2 | Fam | F | N | Y | D | ND | / | / | / | 95%(F) | NARP |  |
| 125 | 8993 | m.8993T\>G | T8993G\-F47 | T8993G\-F47\-II3 | Fam | ND | Y | ND | D | 19 wk gestation | / | / | / | 64%(CVS); 65%(AS1\) | ND | Prenatal diagnosis paper. |
| 126 | 8993 | m.8993T\>G | T8993G\-F48 | T8993G\-F48\-I1 | Uninf | F | N | N | A | ND | 65% | / | / | / | Healthy |  |
| 127 | 8993 | m.8993T\>G | T8993G\-F48 | T8993G\-F48\-II2 | Fam | F | N | Y | A | ND | / | 1 | / | / | NARP |  |
| 128 | 8993 | m.8993T\>G | T8993G\-F48 | T8993G\-F48\-II3 | Fam | ND | N | N | A | 7 y follow\-up | / | / | / | 13%(CVS); 10%(AS1\); 10%(AS2\) | Healthy at 7 years | Prenatal diagnosis paper. |
| 129 | 8993 | m.8993T\>G | T8993G\-F49 | T8993G\-F49\-II6 | Fam | F | N | N | A | ND | 75% | / | / | 77%(BM) | Healthy |  |
| 130 | 8993 | m.8993T\>G | T8993G\-F49 | T8993G\-F49\-III1 | Fam | ND | N | N | A | 4 y follow\-up | / | / | / | 30%(CVS) | Healthy at 4 years | Prenatal diagnosis paper. |
| 131 | 8993 | m.8993T\>G | T8993G\-F49 | T8993G\-F49\-III2 | Fam | ND | N | ND | D | 15 wk gestation | / | / | / | 70%(CVS); 70%(AS1\) | Prenatal intermediate/high mutant load | Prenatal diagnosis paper. |
| 132 | 8993 | m.8993T\>G | T8993G\-F49 | T8993G\-F49\-II7 | Fam | F | N | N | A | ND | 30% | / | / | 38%(BM) | Healthy |  |
| 133 | 8993 | m.8993T\>G | T8993G\-F49 | T8993G\-F49\-III4 | Fam | ND | N | ND | D | 18 wk gestation | / | / | / | 87%(AS1\) | Prenatal high mutant load | Prenatal diagnosis paper. |
| 134 | 8993 | m.8993T\>G | T8993G\-F49 | T8993G\-F49\-III5 | Fam | ND | N | ND | D | 22 wk gestation | / | / | / | 70%(AS1\) | Prenatal intermediate/high mutant load | Prenatal diagnosis paper. |
| 135 | 8993 | m.8993T\>G | T8993G\-F50 | T8993G\-F50\-IV14 | Fam | F | N | N | A | ND | 90% | / | / | / | Healthy |  |
| 136 | 8993 | m.8993T\>G | T8993G\-F50 | T8993G\-F50\-V1 | Fam | M | Y | Y | A | 22mo | 98% | / | / | / | Leigh syndrome |  |
| 137 | 8993 | m.8993T\>G | T8993G\-F50 | T8993G\-F50\-V2 | Fam | F | N | Y | A | ND | / | / | / | / | Progressive neurologic syndrome; mild psychomotor delay; slurred speech; high pyruvate blood concentrations |  |
| 138 | 8993 | m.8993T\>G | T8993G\-F50 | T8993G\-F50\-V3 | Fam | F | N | Y | D | 6 y | / | / | / | / | Severe psychomotor delay; axial hypotonia; slurred speech; elevated lactic acid and ammonia; febrile coma; repetitive seizures |  |
| 139 | 8993 | m.8993T\>G | T8993G\-F50 | T8993G\-F50\-IV16 | Fam | F | N | N | A | ND | 96% | / | / | / | Healthy | Carrying T8741G; A8795G; A9024G |
| 140 | 8993 | m.8993T\>G | T8993G\-F50 | T8993G\-F50\-V4 | Fam | F | N | N | A | ND | 44% | / | / | / | Healthy |  |
| 141 | 8993 | m.8993T\>G | T8993G\-F50 | T8993G\-F50\-V5 | Fam | M | Y | Y | A | 15 | 97% | / | / | / | Leigh syndrome; peripheral neuropathy; hypotonia; ataxia |  |
| 142 | 8993 | m.8993T\>G | T8993G\-F50 | T8993G\-F50\-V6 | Fam | M | N | N | A | ND | 49% | / | / | / | Healthy |  |
| 143 | 8993 | m.8993T\>G | T8993G\-F50 | T8993G\-F50\-IV18 | Fam | F | N | N | A | ND | 60% | / | / | / | Healthy |  |
| 144 | 8993 | m.8993T\>G | T8993G\-F50 | T8993G\-F50\-V7 | Fam | F | N | Y | D | 5mo | / | / | / | / | Psychomotor delay; axial and peripheral hypotonia; high lactate and ammonia |  |
| 145 | 8993 | m.8993T\>G | T8993G\-F50 | T8993G\-F50\-V8 | Fam | M | Y | Y | A | 4mo | 94% | / | / | / | Leigh syndrome |  |
| 146 | 8993 | m.8993T\>G | T8993G\-F50 | T8993G\-F50\-V9 | Fam | M | N | N | A | ND | / | / | / | / | Healthy |  |
| 147 | 8993 | m.8993T\>G | T8993G\-F51 | T8993G\-F51\-II1 | De novo | M | Y | Y | D | 1 | / | 90% | / | / | Leigh syndrome |  |
| 148 | 8993 | m.8993T\>G | T8993G\-F52 | T8993G\-F52\-II1 | De novo | M | Y | Y | D | 5\.5mo | 97% | 97% | / | 96%(F) | Leigh syndrome |  |
| 149 | 8993 | m.8993T\>G | T8993G\-F53 | T8993G\-F53\-II1 | Fam | F | Y | Y | A | 2 | Homo | / | / | Homo(F) | Leigh syndrome |  |
| 150 | 8993 | m.8993T\>G | T8993G\-F53 | T8993G\-F53\-I2 | Uninf | F | N | N | A | 22 | 70% | / | / | 100%(F) | Healthy |  |
| 151 | 8993 | m.8993T\>G | T8993G\-F54 | T8993G\-F54\-II2 | Fam | M | Y | Y | A | 2\.5 | 95% | / | / | 100%(F) | Leigh syndrome |  |
| 152 | 8993 | m.8993T\>G | T8993G\-F54 | T8993G\-F54\-II1 | Fam | F | N | N | A | 1 | 50% | / | / | 62%(F) | Healthy |  |
| 153 | 8993 | m.8993T\>G | T8993G\-F54 | T8993G\-F54\-I2 | Fam | F | N | N | A | 23 | 13% | / | / | 16%(F) | Healthy |  |
| 154 | 8993 | m.8993T\>G | T8993G\-F55 | T8993G\-F55\-III9 | Fam | F | Y | N | A | ND | 24\.50% | / | 33\.65% | 23\.27%(Heart) | Healthy |  |
| 155 | 8993 | m.8993T\>G | T8993G\-F55 | T8993G\-F55\-IV12 | Fam | M | N | N | A | birth | / | / | / | 2\.36\-9\.23%(MULTIPLENEONATALTISSUES) | Healthy |  |
| 156 | 8993 | m.8993T\>G | T8993G\-F55 | T8993G\-F55\-IV10 | Fam | F | N | Y | D | 6y | / | / | / | \>95%(TISSUEND) | Leigh syndrome |  |
| 157 | 8993 | m.8993T\>G | T8993G\-F55 | T8993G\-F55\-IV11 | Fam | M | N | Y | D | 6y | / | / | / | \>95%(TISSUEND) | Leigh syndrome |  |
| 158 | 8993 | m.8993T\>G | T8993G\-F56 | T8993G\-F56\-P1 | Uninf | M | Y | Y | A | 21 | / | / | / | 57%(KIDNEY) | NARP syndrome; renal involvement; FSGS; end\-stage renal disease |  |
| 159 | 8993 | m.8993T\>G | T8993G\-F57 | T8993G\-F57\-III2 | De novo | M | Y | Y | A | 13mo | 1 | / | / | 83%(F) | MILS; developmental regression; lactic acidosis; seizures/infantile spasms; cortical blindness; apnea; gastrostomy |  |
| 160 | 8993 | m.8993T\>G | T8993G\-F58 | T8993G\-F58\-III1 | Uninf | F | N | N | A | ND | 50% | / | / | / | Healthy |  |
| 161 | 8993 | m.8993T\>G | T8993G\-F58 | T8993G\-F58\-IV1 | Fam | M | N | Y | A | ND | 87% | / | / | / | Leigh syndrome |  |
| 162 | 8993 | m.8993T\>G | T8993G\-F58 | T8993G\-F58\-IV2 | Fam | M | N | Y | D | 3mo | 92% | / | / | / | Sudden infant death syndrome |  |
| 163 | 8993 | m.8993T\>G | T8993G\-F58 | T8993G\-F58\-IV3 | Fam | M | Y | Y | D | ND | / | 98% | / | 98%(F) | Leigh syndrome |  |
| 164 | 8993 | m.8993T\>G | T8993G\-F59 | T8993G\-F59\-P1 | Uninf | F | Y | Y | A | 25 | / | / | / | / | Leigh syndrome; severe hearing loss |  |
| 165 | 8993 | m.8993T\>G | T8993G\-F60 | T8993G\-F60\-P1 | Uninf | M | Y | Y | ND | 6mo onset | / | 93% | / | / | Leigh disease; lactic acidosis; severe complex IV deficiency | Family history negative |
| 166 | 8993 | m.8993T\>G | T8993G\-F61 | T8993G\-F61\-P1 | Uninf | M | Y | Y | ND | 1y onset | / | 91% | / | / | Leigh disease; lactic acidosis; severe complex IV deficiency | Family history negative |
| 167 | 8993 | m.8993T\>G | T8993G\-F62 | T8993G\-F62\-P1 | Uninf | F | Y | Y | ND | 4 | \~100% | / | / | / | Leigh syndrome; epileptic seizures; psychomotor retardation; speech delay; muscle weakness; lactate acidosis; abnormal brain MRI | Family history negative |

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