MCID: LGH007
MIFTS: 68

Leigh Syndrome

Categories: Genetic diseases, Rare diseases, Cardiovascular diseases, Neuronal diseases, Eye diseases, Metabolic diseases

Aliases & Classifications for Leigh Syndrome

MalaCards integrated aliases for Leigh Syndrome:

Name: Leigh Syndrome 53 12 49 24 71 36 28 28 28 51
Leigh Disease 12 72 49 24 71 41 14 69
Leigh Syndrome Due to Mitochondrial Complex I Deficiency 53 71 28
Leigh's Disease 49 24 50
Sne 53 49 71
Ls 53 49 71
Leigh Syndrome Due to Mitochondrial Complex Iii Deficiency 71 28
Leigh Syndrome Due to Mitochondrial Complex Ii Deficiency 71 28
Necrotizing Encephalopathy, Infantile Subacute, of Leigh 53 69
Necrotizing Encephalopathy Infantile Subacute of Leigh 49 71
Leigh Syndrome Due to Cytochrome C Oxidase Deficiency 53 13
Infantile Subacute Necrotizing Encephalopathy 49 24
Subacute Necrotizing Encephalomyelopathy 12 24
Cardiomyopathy with Hypotonia Due to Cytochrome C Oxidase Deficiency 55
Maternally-Inherited Infantile Subacute Necrotizing Encephalopathy 55
Necrotizing Encephalopathy, Infantile Subacute, of Leigh; Sne 53
Leigh Syndrome Due to Mitochondrial Complex Iv Deficiency 71
Leigh Syndrome Due to Mitochondrial Complex 1 Deficiency 53
Leigh Syndrome Due to Mitochondrial Complex V Deficiency 71
Leigh Syndrome Due to Mitochondrial Cox4 Deficiency 53
Cardiomyopathy with Myopathy Due to Cox Deficiency 55
Juvenile Subacute Necrotizing Encephalomyelopathy 12
Encephalopathy, Subacute Necrotizing, Infantile 69
Encephalopathy, Subacute Necrotizing, Juvenile 69
Juvenile Subacute Necrotizing Encephalopathy 24
Infantile Necrotizing Encephalomyelopathy 12
Leigh Syndrome, Due to Cox Iv Deficiency 53
Subacute Necrotizing Encephalopathy 49
Maternally Inherited Leigh Syndrome 69
Maternally-Inherited Leigh Syndrome 55
Leigh's Necrotizing Encephalopathy 49
Maternally-Inherited Leigh Disease 55
Leigh Syndrome with Cardiomyopathy 55
Leigh Disease with Myopathy 55
Mils 55

Characteristics:

Orphanet epidemiological data:

55
maternally-inherited leigh syndrome
Inheritance: Mitochondrial inheritance; Age of onset: Childhood,Infancy;

OMIM:

53
Inheritance:
autosomal recessive
mitochondrial

Miscellaneous:
clinical heterogeneity
onset usually in infancy or early childhood
genetic heterogeneity (may be caused by mutation in nuclear-encoded or mitochondrial-encoded genes)
progressive disorder, usually with rapid, relentless course
subset of patients have cytochrome c oxidase deficiency (see )
see also x-linked leigh syndrome
see also french-canadian type of leigh syndrome



Classifications:



Summaries for Leigh Syndrome

NINDS : 50 Leigh's disease is a rare inherited neurometabolic disorder that affects the central nervous system. This progressive disorder begins in infants between the ages of three months and two years. Rarely, it occurs in teenagers and adults. Leigh's disease can be caused by mutations in mitochondrial DNA or by deficiencies of an enzyme called pyruvate dehydrogenase. Symptoms of Leigh's disease usually progress rapidly. The earliest signs may be poor sucking ability,and the loss of head control and motor skills.These symptoms may be accompanied by loss of appetite, vomiting, irritability, continuous crying, and seizures. As the disorder progresses, symptoms may also include generalized weakness, lack of muscle tone, and episodes of lactic acidosis, which can lead to impairment of respiratory and kidney function.   In Leigh’s disease, genetic mutations in mitochondrial DNA interfere with the energy sources that run cells in an area of the brain that plays a role in motor movements. The primary function of mitochondria is to convert the energy in glucose and fatty acids into a substance called adenosine triphosphate ( ATP). The energy in ATP drives virtually all of a cell's metabolic functions. Genetic mutations in mitochondrial DNA, therefore, result in a chronic lack of energy in these cells, which in turn affects the central nervous system and causes progressive degeneration of motor functions. There is also a form of Leigh’s disease (called X-linked Leigh's disease) which is the result of mutations in a gene that produces another group of substances that are important for cell metabolism. This gene is only found on the X chromosome. 

MalaCards based summary : Leigh Syndrome, also known as leigh disease, is related to mitochondrial dna-associated leigh syndrome and narp and leigh syndrome with leukodystrophy, and has symptoms including ataxia, seizures and dystonia. An important gene associated with Leigh Syndrome is SURF1 (SURF1, Cytochrome C Oxidase Assembly Factor), and among its related pathways/superpathways are Oxidative phosphorylation and Pyruvate metabolism. The drugs Cysteamine and Tocopherol have been mentioned in the context of this disorder. Affiliated tissues include cerebellum, spinal cord and thalamus, and related phenotypes are Decreased shRNA abundance (Z-score < -2) and Decreased shRNA abundance (Z-score < -2)

Disease Ontology : 12 A mitochondrial metabolism disease characterized by progressive loss of mental and movement abilities. Symptoms usually begin between ages of three months and two years and include loss of appetite, vomiting, irritability and seizure activity.

Genetics Home Reference : 24 Leigh syndrome is a severe neurological disorder that usually becomes apparent in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within two to three years, usually due to respiratory failure. A small number of individuals do not develop symptoms until adulthood or have symptoms that worsen more slowly.

NIH Rare Diseases : 49 Leigh syndrome is a rare, inheritedneurodegenerative condition. It usually becomes apparent in infancy, often after a viral infection. Rarely, it begins in the teenage or adult years. Signs and symptoms usually progress rapidly. Early symptoms may include poor sucking ability; loss of head control and motor skills; loss of appetite; vomiting; and seizures. As the condition progresses, symptoms may include weakness and lack of muscle tone; spasticity; movement disorders; cerebellar ataxia; and peripheral neuropathy. Complications can lead to impairment of respiratory, heart and kidney function. The term "Leigh-like syndrome" is often used for people with features that are strongly suggestive of Leigh syndrome but who do not meet the diagnostic criteria.  The inheritance of Leigh syndrome depends on where the responsible gene is located in each case. This is because it can be due to mutations in either mitochondrial DNA or nuclear DNA:Mitochondrial DNA-associated Leigh syndrome follows a mitochondrial inheritance pattern (also called maternal inheritance). Nuclear gene-encoded Leigh syndrome may be inherited in an autosomal recessive or X-linked manner. Treatment is based on the symptoms present and depends on the type of Leigh syndrome a person has. While life expectancy depends on the cause of Leigh syndrome in each person, most do not survive past mid-childhood or adolescence. Last updated: 12/27/2016

OMIM : 53 Leigh syndrome is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation. Clinical symptoms depend on which areas of the central nervous system are involved. The most common underlying cause is a defect in oxidative phosphorylation (Dahl, 1998). Leigh syndrome may be a feature of a deficiency of any of the mitochondrial respiratory chain complexes: complex I deficiency (252010), complex II deficiency (252011), complex III deficiency (124000), complex IV deficiency (cytochrome c oxidase; 220110), or complex V deficiency (604273). (256000)

UniProtKB/Swiss-Prot : 71 Leigh syndrome: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia.

Wikipedia : 72 Leigh syndrome (also called Leigh disease and subacute necrotizing encephalomyelopathy) is an... more...

Related Diseases for Leigh Syndrome

Diseases related to Leigh Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 91)
# Related Disease Score Top Affiliating Genes
1 mitochondrial dna-associated leigh syndrome and narp 34.1 MT-ATP6 MT-ND3 MT-ND4 MT-ND5 MT-ND6
2 leigh syndrome with leukodystrophy 33.7 COX15 NDUFA10 NDUFA12 NDUFA2 NDUFA9 NDUFAF2
3 mitochondrial complex i deficiency 33.1 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFA10 NDUFAF2
4 mitochondrial complex iv deficiency 33.0 COX10 COX15 SURF1
5 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 32.2 MT-ATP6 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFAF2
6 neuropathy 30.8 MT-ATP6 MT-ND4 MT-ND5 MT-ND6
7 mitochondrial metabolism disease 30.8 COX10 COX15 MT-ATP6 MT-ND3 MT-ND4 MT-ND5
8 leber hereditary optic neuropathy 30.4 MT-ATP6 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFAF2
9 mitochondrial disorders 30.3 BCS1L COX10 MT-ATP6 MT-ND3 MT-ND4 MT-ND5
10 leigh syndrome, french canadian type 12.5
11 mitochondrial dna-associated leigh syndrome 12.4
12 nuclear gene-encoded leigh syndrome 12.3
13 leigh syndrome with nephrotic syndrome 11.9
14 lichen sclerosus et atrophicus 11.4
15 lichen sclerosus 11.4
16 pyruvate carboxylase deficiency 11.2
17 coenzyme q10 deficiency, primary, 1 11.0
18 3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome 11.0
19 cholestasis, benign recurrent intrahepatic, 2 11.0
20 necrotizing encephalomyelopathy, subacute, of leigh, adult 10.9
21 3-hydroxyisobutyryl-coa hydrolase deficiency 10.8
22 mitochondrial complex ii deficiency 10.8
23 striatonigral degeneration, infantile 10.8
24 striatonigral degeneration, infantile, mitochondrial 10.8
25 coenzyme q10 deficiency, primary, 3 10.8
26 coenzyme q10 deficiency, primary, 5 10.8
27 combined oxidative phosphorylation deficiency 15 10.8
28 mitochondrial complex iii deficiency, nuclear type 2 10.8
29 combined oxidative phosphorylation deficiency 32 10.8
30 parkinson disease 6, autosomal recessive early-onset 10.7 MT-ND5 MT-ND6
31 leber optic atrophy 10.7 MT-ATP6 MT-ND3 MT-ND4 MT-ND5 MT-ND6
32 leber optic atrophy and dystonia 10.7 MT-ND3 MT-ND4 MT-ND6
33 kearns-sayre syndrome 10.7 MT-ATP6 MT-ND4 MT-ND5 MT-ND6 SDHA
34 encephalomyopathy 10.7 MT-ND4 MT-ND5 MT-ND6
35 comedo carcinoma 10.7 NDUFS3 NDUFS4
36 cranial nerve disease 10.7 MT-ND4 MT-ND5 MT-ND6
37 lactic acidosis 10.7 MT-ATP6 MT-ND4 MT-ND5 MT-ND6
38 optic nerve disease 10.7 MT-ND4 MT-ND5 MT-ND6
39 sparganosis 10.6 MT-ND3 MT-ND4
40 orbital cancer 10.6 NDUFA12 NDUFA2
41 mitochondrial myopathy 10.6 MT-ATP6 MT-ND4 MT-ND5
42 cardioencephalomyopathy 10.6 COX15 SURF1
43 mitochondrial encephalomyopathy 10.4 BCS1L MT-ND4 MT-ND5 MT-ND6
44 cortical blindness 10.4 MT-ND4 MT-ND6
45 diphyllobothriasis 10.3 MT-ND3 MT-ND5
46 bell's palsy 10.0
47 branchiootic syndrome 1 9.9
48 leukodystrophy 9.9
49 dystonia 9.9
50 hypoxia 9.9

Graphical network of the top 20 diseases related to Leigh Syndrome:



Diseases related to Leigh Syndrome

Symptoms & Phenotypes for Leigh Syndrome

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
ataxia
seizures
dystonia
spasticity
dysarthria
more
Neurologic Behavioral Psychiatric Manifestations:
emotional lability

Laboratory Abnormalities:
increased serum lactate
increased csf lactate

Respiratory:
respiratory failure
abnormal respiratory patterns

Muscle Soft Tissue:
hypotonia

Head And Neck Eyes:
ophthalmoplegia
ptosis
nystagmus
optic atrophy
strabismus
more
Growth Other:
failure to thrive

Metabolic Features:
lactic acidosis

Skin Nails Hair Hair:
hypertrichosis


Clinical features from OMIM:

256000

Human phenotypes related to Leigh Syndrome:

31 (show all 35)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 hallmark (90%) HP:0001251
2 seizures 31 frequent (33%) HP:0001250
3 dystonia 31 HP:0001332
4 ophthalmoplegia 31 HP:0000602
5 ptosis 31 HP:0000508
6 nystagmus 31 hallmark (90%) HP:0000639
7 emotional lability 31 HP:0000712
8 intellectual disability 31 HP:0001249
9 muscular hypotonia 31 hallmark (90%) HP:0001252
10 spasticity 31 HP:0001257
11 dysarthria 31 HP:0001260
12 hyperreflexia 31 HP:0001347
13 failure to thrive 31 HP:0001508
14 respiratory insufficiency 31 hallmark (90%) HP:0002093
15 global developmental delay 31 HP:0001263
16 sensorineural hearing impairment 31 HP:0000407
17 optic atrophy 31 frequent (33%) HP:0000648
18 cognitive impairment 31 hallmark (90%) HP:0100543
19 abnormality of movement 31 hallmark (90%) HP:0100022
20 hemiplegia/hemiparesis 31 frequent (33%) HP:0004374
21 strabismus 31 hallmark (90%) HP:0000486
22 increased serum lactate 31 HP:0002151
23 lactic acidosis 31 HP:0003128
24 respiratory failure 31 HP:0002878
25 abnormal pattern of respiration 31 HP:0002793
26 generalized hypotonia 31 HP:0001290
27 gliosis 31 HP:0002171
28 pigmentary retinopathy 31 HP:0000580
29 hypertrichosis 31 HP:0000998
30 increased csf lactate 31 HP:0002490
31 progressive spastic paraplegia 31 frequent (33%) HP:0007020
32 hepatocellular necrosis 31 HP:0001404
33 cns demyelination 31 HP:0007305
34 progressive ophthalmoplegia 31 frequent (33%) HP:0007650
35 decreased activity of mitochondrial respiratory chain 31 hallmark (90%) HP:0008972

UMLS symptoms related to Leigh Syndrome:


seizures, ophthalmoplegia, muscle spasticity, ataxia

GenomeRNAi Phenotypes related to Leigh Syndrome according to GeneCards Suite gene sharing:

25 (show all 41)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-111 10.07 NDUFS7
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 10.07 NDUFS7 NDUFA9 BCS1L COX10 NDUFA10
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-119 10.07 COX10
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 10.07 BCS1L
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-173 10.07 BCS1L
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-193 10.07 NDUFA10
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-206 10.07 NDUFS7 NDUFA10
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 10.07 NDUFA9 NDUFS7 BCS1L COX10
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-26 10.07 BCS1L
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-34 10.07 NDUFA9
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-40 10.07 BCS1L
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 10.07 BCS1L
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-66 10.07 NDUFA10
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-71 10.07 NDUFA10
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-72 10.07 COX10
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-75 10.07 NDUFA9
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-86 10.07 COX10
18 Decreased shRNA abundance (Z-score < -2) GR00366-A-98 10.07 NDUFA9
19 Increased shRNA abundance (Z-score > 2) GR00366-A-102 9.8 NDUFS7
20 Increased shRNA abundance (Z-score > 2) GR00366-A-107 9.8 NDUFA10
21 Increased shRNA abundance (Z-score > 2) GR00366-A-11 9.8 NDUFA2
22 Increased shRNA abundance (Z-score > 2) GR00366-A-114 9.8 NDUFA2
23 Increased shRNA abundance (Z-score > 2) GR00366-A-115 9.8 NDUFS7 NDUFA10 NDUFA9
24 Increased shRNA abundance (Z-score > 2) GR00366-A-120 9.8 NDUFS7 NDUFA10
25 Increased shRNA abundance (Z-score > 2) GR00366-A-129 9.8 NDUFA9
26 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.8 NDUFA2
27 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.8 NDUFS7
28 Increased shRNA abundance (Z-score > 2) GR00366-A-162 9.8 NDUFA2
29 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.8 NDUFA9 NDUFA10
30 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.8 NDUFA10
31 Increased shRNA abundance (Z-score > 2) GR00366-A-176 9.8 NDUFA10
32 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.8 NDUFS7 NDUFA2
33 Increased shRNA abundance (Z-score > 2) GR00366-A-183 9.8 NDUFA10
34 Increased shRNA abundance (Z-score > 2) GR00366-A-57 9.8 NDUFA9 NDUFS7 NDUFA10 NDUFA2
35 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.8 NDUFA10
36 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.8 NDUFA9
37 Increased shRNA abundance (Z-score > 2) GR00366-A-76 9.8 NDUFA10
38 Increased shRNA abundance (Z-score > 2) GR00366-A-81 9.8 NDUFA9
39 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.8 NDUFA2
40 Increased shRNA abundance (Z-score > 2) GR00366-A-9 9.8 NDUFA2
41 Decreased shRNA abundance GR00297-A 9.63 COX10 NDUFA10 NDUFS3 NDUFS7 NDUFS8 SDHA

Drugs & Therapeutics for Leigh Syndrome

Drugs for Leigh Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 10)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cysteamine Approved, Investigational Phase 2 60-23-1 6058
2 Tocopherol Approved, Investigational, Nutraceutical Phase 2
3
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
4 Micronutrients Phase 2
5 Trace Elements Phase 2
6 Ubiquinone Phase 2
7 Tocopherols Phase 2
8 Tocotrienol, alpha Phase 2
9 Tocotrienols Phase 2
10 Tocotrienol Investigational, Nutraceutical Phase 2 6829-55-6

Interventional clinical trials:

(show all 11)

# Name Status NCT ID Phase Drugs
1 EPI-743 for Mitochondrial Respiratory Chain Diseases Unknown status NCT01370447 Phase 2 EPI-743
2 Safety and Efficacy Study of EPI-743 in Children With Leigh Syndrome Completed NCT01721733 Phase 2 Placebo;EPI-743 15 mg/kg;EPI-743 5 mg/kg
3 Open-Label, Dose-Escalating Study Assessing Safety, Tolerability, Efficacy, of RP103 in Mitochondrial Disease Completed NCT02023866 Phase 2 Cysteamine Bitartrate
4 The KHENERGY Study Completed NCT02909400 Phase 2 KH176;placebo
5 A Long-Term Extension Study of RP103-MITO-001 (NCT02023866) to Assess RP103 in Children With Inherited Mitochondrial Disease Completed NCT02473445 Phase 2 Cysteamine Bitartrate Delayed-release Capsules
6 Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome Enrolling by invitation NCT02352896 Phase 2 EPI-743
7 A Dose-escalating Clinical Trial With KH176 Completed NCT02544217 Phase 1 KH176;placebo
8 The Leigh Syndrome Registry Recruiting NCT03137355
9 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168
10 North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC) Recruiting NCT01694940
11 Tissue Sample Study for Mitochondrial Disorders Enrolling by invitation NCT01803906

Search NIH Clinical Center for Leigh Syndrome

Cochrane evidence based reviews: leigh disease

Genetic Tests for Leigh Syndrome

Genetic tests related to Leigh Syndrome:

# Genetic test Affiliating Genes
1 Leigh Syndrome (nuclear Dna Mutation) 28
2 Leigh Syndrome 28 BCS1L COX10 COX15 FOXRED1 NDUFA10 NDUFA12 NDUFA2 NDUFA9 NDUFAF2 NDUFAF6 NDUFS3 NDUFS4 NDUFS7 NDUFS8 SDHA SURF1
3 Leigh Syndrome Due to Mitochondrial Complex I Deficiency 28
4 Leigh Syndrome Due to Mitochondrial Complex Ii Deficiency 28
5 Leigh Syndrome (mtdna Mutation) 28
6 Leigh Syndrome Due to Mitochondrial Complex Iii Deficiency 28

Anatomical Context for Leigh Syndrome

MalaCards organs/tissues related to Leigh Syndrome:

38
Cerebellum, Spinal Cord, Thalamus, Kidney, Eye, Brain, Heart

Publications for Leigh Syndrome

Articles related to Leigh Syndrome:

(show top 50) (show all 221)
# Title Authors Year
1
The cerebellum is a common site of affection in Leigh syndrome. ( 28963669 )
2018
2
Perioperative risk assessment for successful kidney transplant in leigh syndrome: a case report. ( 29390978 )
2018
3
Phenotype-genotype correlations in Leigh syndrome: new insights from a multicentre study of 96 patients. ( 29101127 )
2018
4
Leigh syndrome in individuals bearing m.9185T>C MTATP6 variant. Is hyperventilation a factor which starts its development? ( 29116603 )
2018
5
The Cerebellum Is a Common Site of Affection in Leigh Syndrome. ( 29056245 )
2018
6
Correction for Ferrari et al., Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome. ( 29382743 )
2018
7
Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome. ( 28777931 )
2017
8
Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome. ( 28483998 )
2017
9
Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients. ( 28429146 )
2017
10
Involvement of Cerebellum in Leigh Syndrome: Case Report and Review of the Literature. ( 28739363 )
2017
11
Novel mutation of ND4 gene identified by targeted next-generation sequencing in patient with Leigh syndrome. ( 27761019 )
2017
12
Loss of Mitochondrial Ndufs4 in Striatal Medium Spiny Neurons Mediates Progressive Motor Impairment in a Mouse Model of Leigh Syndrome. ( 28883788 )
2017
13
Premature Ovarian Failure in French Canadian Leigh Syndrome. ( 28284481 )
2017
14
AAV9-based gene therapy partially ameliorates the clinical phenotype of a mouse model of Leigh syndrome. ( 28753212 )
2017
15
Correction for Ferrari et al., Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome. ( 28584118 )
2017
16
Complete mtDNA sequencing reveals mutations m.9185T>C and m.13513G>A in three patients with Leigh syndrome. ( 29228836 )
2017
17
Japanese Leigh syndrome case treated with EPI-743. ( 28916229 )
2017
18
Bioenergetic Impairment in Congenital Muscular Dystrophy Type 1A and Leigh Syndrome Muscle Cells. ( 28367954 )
2017
19
Why does Leigh syndrome respond to immunotherapy? ( 28649511 )
2017
20
Head Trauma as a Precipitating Factor for Late-onset Leigh Syndrome: a Case Report. ( 28286850 )
2017
21
Novel LRPPRC Mutation in a Boy With Mild Leigh Syndrome, French-Canadian Type Outside of QuAcbec. ( 29152527 )
2017
22
Defective mitochondrial RNA processing due to PNPT1 variants causes Leigh syndrome. ( 28645153 )
2017
23
Management of Leigh Syndrome: current status and new insights. ( 28905387 )
2017
24
NDUFAF4 variants are associated with Leigh syndrome and cause a specific mitochondrial complex I assembly defect. ( 28853723 )
2017
25
Do lesional perfusion abnormalities on arterial spin labeling truly contribute to the diagnosis of Leigh syndrome? ( 27826676 )
2017
26
Direct effects of mitochondrial dysfunction on poor bone health in Leigh syndrome. ( 28899781 )
2017
27
Widening the Heterogeneity of Leigh Syndrome: Clinical, Biochemical, and Neuroradiologic Features in a Patient Harboring a NDUFA10 Mutation. ( 28247337 )
2017
28
Response to correspondence of NDUFS4-related Leigh syndrome in Hutterites. ( 28371264 )
2017
29
Schizophrenia-like symptoms in a patient with Leigh syndrome. ( 28262162 )
2017
30
Fatigable ptosis as an initial presentation of adult-onset Leigh syndrome. ( 29038134 )
2017
31
Modulation of mitochondrial dysfunction-related oxidative stress in fibroblasts of patients with Leigh syndrome by inhibition of prooxidative p66Shc pathway. ( 28739512 )
2017
32
Orbital rhabdomyosarcoma in a child with Leigh syndrome. ( 29274371 )
2017
33
NDUFS4-related Leigh syndrome in Hutterites. ( 28371352 )
2017
34
Is vatiquinone truly beneficial for Leigh syndrome? ( 29054334 )
2017
35
Traumatic brain injury is unlikely precipitating Leigh syndrome due to the GJB2 mutation c.35delG. ( 29201956 )
2017
36
Generation of a human iPSC line from a patient with Leigh syndrome. ( 27345786 )
2016
37
Ophthalmological characteristics in children with Leigh syndrome - A long-term follow-up. ( 26893257 )
2016
38
Response to letter to the editor: Why does Leigh syndrome responds to immunotherapy? ( 27547733 )
2016
39
Whole Exome Sequencing Identifies the Genetic Basis of Late-Onset Leigh Syndrome in a Patient with MRI but Little Biochemical Evidence of a Mitochondrial Disorder. ( 27344648 )
2016
40
DNM1L-related encephalopathy in infancy with Leigh syndrome-like phenotype and suppression-burst. ( 27301544 )
2016
41
The neuroimaging of Leigh syndrome: case series and review of the literature. ( 26739140 )
2016
42
Bilateral striatal necrosis caused by ADAR mutations in two siblings with dystonia and freckles-like skin changes that should be differentiated from Leigh syndrome. ( 28139822 )
2016
43
Generation of a human iPSC line from a patient with Leigh syndrome caused by a mutation in the MT-ATP6 gene. ( 27346203 )
2016
44
Leigh syndrome associated with a novel mutation in the COX15 gene. ( 26959537 )
2016
45
Ndufs4 related Leigh syndrome: A case report and review of the literature. ( 27079373 )
2016
46
FDG-PET study of patients with Leigh syndrome. ( 26944169 )
2016
47
Ophthalmologic involvement in Leigh syndrome. ( 27234010 )
2016
48
Free-thiamine is a potential biomarker of thiamine transporter-2 deficiency: a treatable cause of Leigh syndrome. ( 26657515 )
2016
49
The pleiotropic effects of decanoic acid treatment on mitochondrial function in fibroblasts from patients with complex I deficient Leigh syndrome. ( 27080638 )
2016
50
Significance of rostral brain lesions of Leigh syndrome associated with the mitochondrial DNA 8993T>G mutation. ( 27206685 )
2016

Variations for Leigh Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Leigh Syndrome:

71 (show all 35)
# Symbol AA change Variation ID SNP ID
1 COX15 p.Arg217Trp VAR_019596 rs28939711
2 COX15 p.Ser344Pro VAR_033117 rs397514662
3 MT-ATP6 p.Leu156Arg VAR_000793 rs199476133
4 MT-ATP6 p.Leu156Pro VAR_000794 rs199476133
5 MT-ATP6 p.Leu217Pro VAR_000797 rs199476135
6 MT-ATP6 p.Leu220Pro VAR_073700 rs199476138
7 MT-ND3 p.Ala47Thr VAR_035092 rs267606891
8 MT-ND5 p.Phe124Leu VAR_035424 rs267606893
9 MT-ND5 p.Ser250Cys VAR_035429 rs267606896
10 NARS2 p.Asn381Ser VAR_073724
11 NDUFA10 p.Gln142Arg VAR_078937 rs387906873
12 NDUFA9 p.Arg321Pro VAR_078936 rs199592341
13 NDUFAF5 p.Leu159Phe VAR_067956 rs267606689
14 NDUFAF5 p.Gly250Val VAR_076864 rs757043077
15 NDUFS4 p.Asp119His VAR_078946 rs747359752
16 NDUFS8 p.Pro79Leu VAR_019538 rs28939679
17 NDUFS8 p.Arg102His VAR_019539 rs121912638
18 NDUFV1 p.Thr423Met VAR_008847 rs121913659
19 POLG p.Gly848Ser VAR_023675 rs113994098
20 POLG p.Arg232His VAR_058871 rs113994093
21 SCO2 p.Gly193Ser VAR_076281 rs759452074
22 SCO2 p.Met258Thr VAR_076282
23 SDHA p.Arg554Trp VAR_002449 rs9809219
24 SDHA p.Ala524Val VAR_016878 rs137852767
25 SDHA p.Cys189Gly VAR_074022
26 SURF1 p.Gly124Glu VAR_007450 rs28933402
27 SURF1 p.Ile246Thr VAR_007452
28 SURF1 p.Gly124Arg VAR_015258 rs782033035
29 SURF1 p.Tyr274Asp VAR_015259 rs121918658
30 SURF1 p.Leu90Pro VAR_068649 rs782024654
31 SURF1 p.Val177Gly VAR_068650
32 SURF1 p.Gly205Glu VAR_068651
33 SURF1 p.Met235Thr VAR_068652
34 SURF1 p.Ala248Asp VAR_068653
35 SURF1 p.Gly257Arg VAR_068654

ClinVar genetic disease variations for Leigh Syndrome:

6 (show top 50) (show all 97)
# Gene Variation Type Significance SNP ID Assembly Location
1 MT-TV m.1624C> T single nucleotide variant Pathogenic rs199476144 GRCh37 Chromosome MT, 1624: 1624
2 MT-TW m.5537_5538insT insertion Pathogenic rs199474672 GRCh37 Chromosome MT, 5537: 5538
3 MT-TK m.8363G> A single nucleotide variant Pathogenic rs118192100 GRCh37 Chromosome MT, 8363: 8363
4 MT-TL1 m.3243A> G single nucleotide variant Pathogenic rs199474657 GRCh37 Chromosome MT, 3243: 3243
5 MT-ATP6 m.8993T> G single nucleotide variant Pathogenic rs199476133 GRCh37 Chromosome MT, 8993: 8993
6 MT-ATP6 m.8993T> C single nucleotide variant Pathogenic rs199476133 GRCh37 Chromosome MT, 8993: 8993
7 MT-ATP6 m.9176T> C single nucleotide variant Pathogenic rs199476135 GRCh37 Chromosome MT, 9176: 9176
8 MT-ATP6 m.8851T> C single nucleotide variant Pathogenic rs199476136 GRCh37 Chromosome MT, 8851: 8851
9 MT-ATP6 m.9185T> C single nucleotide variant Pathogenic rs199476138 GRCh37 Chromosome MT, 9185: 9185
10 MT-ATP6 m.9176T> G single nucleotide variant Pathogenic rs199476135 GRCh37 Chromosome MT, 9176: 9176
11 MT-CO3 m.9537dupC duplication Pathogenic rs267606614 GRCh37 Chromosome MT, 9537: 9537
12 MT-ND6 NC_012920.1: m.14484T> C single nucleotide variant Pathogenic/Likely pathogenic rs199476104 GRCh37 Chromosome MT, 14484: 14484
13 MT-ND6 m.14459G> A single nucleotide variant Pathogenic rs199476105 GRCh37 Chromosome MT, 14459: 14459
14 MT-ND6 m.14487T> C single nucleotide variant Pathogenic rs199476109 GRCh37 Chromosome MT, 14487: 14487
15 MT-ND5 m.12706T> C single nucleotide variant Pathogenic rs267606893 GRCh37 Chromosome MT, 12706: 12706
16 MT-ND5 m.13045A> C single nucleotide variant Pathogenic rs267606895 GRCh37 Chromosome MT, 13045: 13045
17 MT-ND5 m.13084A> T single nucleotide variant Pathogenic rs267606896 GRCh37 Chromosome MT, 13084: 13084
18 MT-ND5; MT-TL1 m.13513G> A single nucleotide variant Pathogenic rs267606897 GRCh37 Chromosome MT, 13513: 13513
19 MT-ND5 m.13042G> A single nucleotide variant Pathogenic rs267606898 GRCh37 Chromosome MT, 13042: 13042
20 MT-ND4 m.11777C> A single nucleotide variant Pathogenic rs28384199 GRCh37 Chromosome MT, 11777: 11777
21 MT-ND3 m.10191T> C single nucleotide variant Pathogenic rs267606890 GRCh37 Chromosome MT, 10191: 10191
22 MT-ND3 m.10158T> C single nucleotide variant Pathogenic rs199476117 GRCh37 Chromosome MT, 10158: 10158
23 MT-ND3 m.10197G> A single nucleotide variant Pathogenic rs267606891 GRCh37 Chromosome MT, 10197: 10197
24 MT-ND2 m.4681T> C single nucleotide variant Pathogenic rs267606889 GRCh37 Chromosome MT, 4681: 4681
25 MT-ND1 NC_012920.1: m.3460G> A single nucleotide variant Pathogenic rs199476118 GRCh37 Chromosome MT, 3460: 3460
26 SURF1 SURF1, 1-BP INS, 868T insertion Pathogenic
27 SURF1 SURF1, IVS5DS, T-G, +2 single nucleotide variant Pathogenic
28 SURF1 SURF1, 2-BP DEL, 550AG deletion Pathogenic
29 SURF1 SURF1, 765C-T single nucleotide variant Pathogenic
30 SURF1 SURF1, IVS4, T-C, +2 single nucleotide variant Pathogenic
31 SURF1 SURF1, 2-BP INS/10-BP DEL, NT326 indel Pathogenic
32 SURF1 SURF1, 2-BP DEL, 855CT deletion Pathogenic
33 SURF1 SURF1, 1-BP INS, 882T insertion Pathogenic
34 SURF1 NM_003172.3(SURF1): c.751C> T (p.Gln251Ter) single nucleotide variant Pathogenic rs121918657 GRCh37 Chromosome 9, 136219301: 136219301
35 SURF1 NM_003172.3(SURF1): c.820T> G (p.Tyr274Asp) single nucleotide variant Pathogenic rs121918658 GRCh37 Chromosome 9, 136218929: 136218929
36 SURF1 SURF1, 2-BP DEL, 790AG deletion Pathogenic
37 SURF1 NM_003172.3(SURF1): c.371G> A (p.Gly124Glu) single nucleotide variant Pathogenic rs28933402 GRCh37 Chromosome 9, 136220748: 136220748
38 SURF1 SURF1, 4-BP INS, 572CCCT insertion Pathogenic
39 SURF1 NM_003172.3(SURF1): c.845_846delCT (p.Ser282Cysfs) deletion Pathogenic rs782316919 GRCh37 Chromosome 9, 136218825: 136218826
40 SURF1 NM_003172.3(SURF1): c.679T> C (p.Trp227Arg) single nucleotide variant Pathogenic rs398122806 GRCh37 Chromosome 9, 136219373: 136219373
41 NDUFA9 NM_005002.4(NDUFA9): c.962G> C (p.Arg321Pro) single nucleotide variant Pathogenic rs199592341 GRCh37 Chromosome 12, 4794490: 4794490
42 NDUFA10 NM_004544.3(NDUFA10): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic rs387906872 GRCh37 Chromosome 2, 240964718: 240964718
43 NDUFA10 NM_004544.3(NDUFA10): c.425A> G (p.Gln142Arg) single nucleotide variant Pathogenic rs387906873 GRCh37 Chromosome 2, 240960649: 240960649
44 NDUFA12 NM_018838.4(NDUFA12): c.178C> T (p.Arg60Ter) single nucleotide variant Pathogenic rs387907139 GRCh37 Chromosome 12, 95388025: 95388025
45 MTFMT NM_139242.3(MTFMT): c.626C> T (p.Ser209Leu) single nucleotide variant Pathogenic/Likely pathogenic rs201431517 GRCh37 Chromosome 15, 65313871: 65313871
46 MTFMT NM_139242.3(MTFMT): c.994C> T (p.Arg332Ter) single nucleotide variant Pathogenic rs200286768 GRCh37 Chromosome 15, 65295576: 65295576
47 MT-ATP6 m.9191T> C single nucleotide variant Pathogenic rs386829069 GRCh37 Chromosome MT, 9191: 9191
48 NDUFS4 NM_002495.3(NDUFS4): c.462delA (p.Lys154Asnfs) deletion Pathogenic rs587776949 GRCh38 Chromosome 5, 53683155: 53683155
49 COX15 NM_004376.6(COX15): c.1030T> C (p.Ser344Pro) single nucleotide variant Pathogenic/Likely pathogenic rs397514662 GRCh37 Chromosome 10, 101476176: 101476176
50 COX15 COX15, SER151TER undetermined variant Pathogenic

Expression for Leigh Syndrome

Search GEO for disease gene expression data for Leigh Syndrome.

Pathways for Leigh Syndrome

Pathways related to Leigh Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 Oxidative phosphorylation hsa00190
2 Pyruvate metabolism hsa00620

GO Terms for Leigh Syndrome

Cellular components related to Leigh Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial membrane GO:0031966 9.92 COX10 COX15 MT-ND3 MT-ND4 MT-ND6 NDUFA2
2 mitochondrial matrix GO:0005759 9.83 NDUFA10 NDUFA9 NDUFS3 NDUFS7 NDUFS8
3 respiratory chain GO:0070469 9.73 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFA10 NDUFA12
4 myelin sheath GO:0043209 9.65 NDUFA10 NDUFS3 SDHA
5 mitochondrial respiratory chain GO:0005746 9.46 COX15 SURF1
6 cytochrome complex GO:0070069 9.4 COX10 COX15
7 mitochondrial respiratory chain complex I GO:0005747 9.36 MT-ND3 MT-ND4 MT-ND5 NDUFA10 NDUFA12 NDUFA2
8 membrane GO:0016020 10.3 BCS1L COX10 COX15 MT-ATP6 MT-ND3 MT-ND4
9 mitochondrion GO:0005739 10.21 BCS1L COX10 COX15 MT-ND3 MT-ND4 MT-ND5
10 mitochondrial inner membrane GO:0005743 10.11 BCS1L COX10 COX15 MT-ATP6 MT-ND3 MT-ND4

Biological processes related to Leigh Syndrome according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 mitochondrial respiratory chain complex I assembly GO:0032981 9.83 BCS1L MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFA10
2 response to oxidative stress GO:0006979 9.72 MT-ND3 NDUFA12 NDUFS8
3 electron transport chain GO:0022900 9.67 NDUFA12 NDUFS4 SDHA SURF1
4 hydrogen ion transmembrane transport GO:1902600 9.65 COX10 COX15 SURF1
5 cellular respiration GO:0045333 9.65 COX10 COX15 NDUFAF2 NDUFS3 NDUFS4
6 reactive oxygen species metabolic process GO:0072593 9.61 NDUFAF2 NDUFS3 NDUFS4
7 ATP biosynthetic process GO:0006754 9.57 MT-ATP6 SURF1
8 aerobic respiration GO:0009060 9.56 COX10 SURF1
9 mitochondrial electron transport, cytochrome c to oxygen GO:0006123 9.54 COX10 COX15
10 respiratory electron transport chain GO:0022904 9.52 NDUFAF2 SDHA
11 heme biosynthetic process GO:0006783 9.51 COX10 COX15
12 respiratory chain complex IV assembly GO:0008535 9.5 COX10 COX15 SURF1
13 mitochondrial respiratory chain complex IV assembly GO:0033617 9.49 BCS1L SURF1
14 ATP synthesis coupled electron transport GO:0042773 9.46 MT-ND4 MT-ND5
15 heme a biosynthetic process GO:0006784 9.4 COX10 COX15
16 mitochondrial electron transport, NADH to ubiquinone GO:0006120 9.4 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFA10 NDUFA12
17 oxidation-reduction process GO:0055114 10.03 COX15 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFA10

Molecular functions related to Leigh Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.76 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFS3 NDUFS7
2 electron transfer activity GO:0009055 9.62 NDUFA12 NDUFAF2 NDUFS3 SDHA
3 cytochrome-c oxidase activity GO:0004129 9.54 COX10 COX15 SURF1
4 NADH dehydrogenase (ubiquinone) activity GO:0008137 9.44 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFA10 NDUFA12
5 oxidoreductase activity, acting on NAD(P)H GO:0016651 9.43 NDUFS3 NDUFS4 NDUFS8
6 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.4 COX15 SDHA
7 NADH dehydrogenase activity GO:0003954 9.35 MT-ND5 NDUFA9 NDUFS3 NDUFS7 NDUFS8

Sources for Leigh Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
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50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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