MCID: LGH007
MIFTS: 67

Leigh Syndrome

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

Aliases & Classifications for Leigh Syndrome

MalaCards integrated aliases for Leigh Syndrome:

Name: Leigh Syndrome 57 12 53 25 75 37 29 29 29 55 6 40
Leigh Disease 12 76 53 25 75 44 15 73
Leigh Syndrome Due to Mitochondrial Complex I Deficiency 57 75 29 6
Leigh Syndrome Due to Mitochondrial Complex Iii Deficiency 75 29 6
Leigh's Disease 53 25 54
Sne 57 53 75
Ls 57 53 75
Leigh Syndrome Due to Mitochondrial Complex Iv Deficiency 75 6
Necrotizing Encephalopathy, Infantile Subacute, of Leigh 57 73
Necrotizing Encephalopathy Infantile Subacute of Leigh 53 75
Leigh Syndrome Due to Cytochrome C Oxidase Deficiency 57 13
Infantile Subacute Necrotizing Encephalopathy 53 25
Subacute Necrotizing Encephalomyelopathy 12 25
Cardiomyopathy with Hypotonia Due to Cytochrome C Oxidase Deficiency 59
Maternally-Inherited Infantile Subacute Necrotizing Encephalopathy 59
Necrotizing Encephalopathy, Infantile Subacute, of Leigh; Sne 57
Leigh Syndrome Due to Mitochondrial Complex Ii Deficiency 75
Leigh Syndrome Due to Mitochondrial Complex 1 Deficiency 57
Leigh Syndrome Due to Mitochondrial Complex V Deficiency 75
Leigh Syndrome Due to Mitochondrial Cox4 Deficiency 57
Cardiomyopathy with Myopathy Due to Cox Deficiency 59
Juvenile Subacute Necrotizing Encephalomyelopathy 12
Encephalopathy, Subacute Necrotizing, Infantile 73
Encephalopathy, Subacute Necrotizing, Juvenile 73
Juvenile Subacute Necrotizing Encephalopathy 25
Infantile Necrotizing Encephalomyelopathy 12
Leigh Syndrome, Due to Cox Iv Deficiency 57
Leigh Syndrome Due to Cox Iv Deficiency 6
Subacute Necrotizing Encephalopathy 53
Maternally Inherited Leigh Syndrome 73
Maternally-Inherited Leigh Syndrome 59
Leigh's Necrotizing Encephalopathy 53
Maternally-Inherited Leigh Disease 59
Leigh Syndrome with Cardiomyopathy 59
Leigh Disease with Myopathy 59
Mils 59

Characteristics:

Orphanet epidemiological data:

59
maternally-inherited leigh syndrome
Inheritance: Mitochondrial inheritance; Age of onset: Childhood,Infancy;

OMIM:

57
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 : 54 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, muscle spasticity and ophthalmoplegia. 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 ptosis and nystagmus

OMIM : 57 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 : 75 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.

NIH Rare Diseases : 53 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.

Genetics Home Reference : 25 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.

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.

Wikipedia : 76 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 103)
# Related Disease Score Top Affiliating Genes
1 mitochondrial dna-associated leigh syndrome and narp 35.0 MT-ATP6 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
2 leigh syndrome with leukodystrophy 34.5 COX15 NDUFA10 NDUFA12 NDUFA2 NDUFA9 NDUFAF6
3 mitochondrial complex iv deficiency 34.0 COX10 COX15 MT-ND3 SURF1
4 mitochondrial complex i deficiency 33.9 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFA10
5 striatonigral degeneration, infantile, mitochondrial 33.2 MT-ATP6 MT-ND3 MT-ND4
6 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 33.2 MT-ATP6 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
7 striatonigral degeneration, infantile 33.2 MT-ATP6 MT-ND3 MT-ND4
8 mitochondrial disorders 31.9 BCS1L COX10 MT-ATP6 MT-ND1 MT-ND3 MT-ND4
9 mitochondrial metabolism disease 31.8 COX15 MT-ATP6 MT-ND3 MT-ND5 MT-ND6 NDUFAF6
10 neuropathy 31.7 MT-ATP6 MT-ND1 MT-ND4 MT-ND6
11 myopathy 31.5 COX10 MT-ATP6 MT-ND1 MT-ND3 MT-ND4 MT-ND5
12 mitochondrial myopathy 31.4 MT-ATP6 MT-ND1 MT-ND4 MT-ND5 MT-ND6
13 optic nerve disease 31.3 MT-ND1 MT-ND4 MT-ND5 MT-ND6
14 leber hereditary optic neuropathy 31.3 MT-ATP6 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
15 leigh syndrome, french canadian type 12.5
16 mitochondrial dna-associated leigh syndrome 12.4
17 nuclear gene-encoded leigh syndrome 12.3
18 leigh syndrome with nephrotic syndrome 11.9
19 lichen sclerosus et atrophicus 11.4
20 lichen sclerosus 11.4
21 leber optic atrophy and dystonia 11.3 MT-ND1 MT-ND3 MT-ND4 MT-ND6
22 deafness, nonsyndromic sensorineural, mitochondrial 11.3 MT-ATP6 MT-ND1 MT-ND4 MT-ND5
23 familial colorectal cancer 11.3 MT-ATP6 MT-ND3 MT-ND4 MT-ND5 MT-ND6
24 leber optic atrophy 11.3 MT-ATP6 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
25 kearns-sayre syndrome 11.3 MT-ATP6 MT-ND1 MT-ND4 MT-ND5 MT-ND6 SDHA
26 myopathy, lactic acidosis, and sideroblastic anemia 3 11.3 MT-ATP6 MT-ND3 MT-ND4
27 encephalomyopathy 11.3 MT-ND1 MT-ND4 MT-ND5 MT-ND6
28 mitochondrial encephalomyopathy 11.3 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
29 cranial nerve disease 11.2 MT-ND1 MT-ND4 MT-ND5 MT-ND6
30 ataxia and polyneuropathy, adult-onset 11.2 MT-ATP6 MT-ND3 MT-ND4
31 lactic acidosis 11.2 MT-ATP6 MT-ND1 MT-ND4 MT-ND5 MT-ND6
32 myopathy, lactic acidosis, and sideroblastic anemia 11.2 MT-ATP6 MT-ND3 MT-ND4
33 pyruvate carboxylase deficiency 11.2
34 sparganosis 11.2 MT-ND3 MT-ND4
35 comedo carcinoma 11.2 NDUFS3 NDUFS4
36 cardiomyopathy, infantile hypertrophic 11.1 MT-ATP6 MT-ND3
37 balanitis xerotica obliterans 11.1
38 aceruloplasminemia 11.1 BCS1L MT-ATP6 SURF1
39 parkinson disease 6, autosomal recessive early-onset 11.1 MT-ND5 MT-ND6
40 orbital cancer 11.1 NDUFA12 NDUFA2
41 cardioencephalomyopathy 11.0 COX15 SURF1
42 coenzyme q10 deficiency, primary, 1 11.0
43 3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome 11.0
44 cholestasis, benign recurrent intrahepatic, 2 11.0
45 cortical blindness 11.0 MT-ND4 MT-ND6
46 mitochondrial dna depletion syndrome 1 10.9 MT-ATP6 MT-ND3
47 necrotizing encephalomyelopathy, subacute, of leigh, adult 10.9
48 3-hydroxyisobutyryl-coa hydrolase deficiency 10.8
49 mitochondrial complex ii deficiency 10.8
50 coenzyme q10 deficiency, primary, 3 10.8

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:

57
Head And Neck Eyes:
ptosis
nystagmus
optic atrophy
strabismus
ophthalmoplegia
more
Neurologic Central Nervous System:
seizures
ataxia
spasticity
dysarthria
hyperreflexia
more
Laboratory Abnormalities:
increased serum lactate
increased csf lactate

Respiratory:
respiratory failure
abnormal respiratory patterns

Muscle Soft Tissue:
hypotonia

Neurologic Behavioral Psychiatric Manifestations:
emotional lability

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:

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

UMLS symptoms related to Leigh Syndrome:


ataxia, muscle spasticity, ophthalmoplegia, seizures

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

26 (show all 27)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-102 10.15 NDUFS7 COX10
2 Increased shRNA abundance (Z-score > 2) GR00366-A-107 10.15 NDUFA10 COX10
3 Increased shRNA abundance (Z-score > 2) GR00366-A-11 10.15 BCS1L NDUFA2
4 Increased shRNA abundance (Z-score > 2) GR00366-A-114 10.15 NDUFA2
5 Increased shRNA abundance (Z-score > 2) GR00366-A-115 10.15 NDUFS7 NDUFA9 NDUFA10
6 Increased shRNA abundance (Z-score > 2) GR00366-A-116 10.15 NDUFS7 NDUFA9 NDUFA10 BCS1L COX10
7 Increased shRNA abundance (Z-score > 2) GR00366-A-120 10.15 NDUFS7 NDUFA10
8 Increased shRNA abundance (Z-score > 2) GR00366-A-129 10.15 NDUFA9
9 Increased shRNA abundance (Z-score > 2) GR00366-A-132 10.15 NDUFA2
10 Increased shRNA abundance (Z-score > 2) GR00366-A-16 10.15 NDUFS7
11 Increased shRNA abundance (Z-score > 2) GR00366-A-161 10.15 BCS1L
12 Increased shRNA abundance (Z-score > 2) GR00366-A-162 10.15 NDUFA2
13 Increased shRNA abundance (Z-score > 2) GR00366-A-166 10.15 NDUFA9 NDUFA10
14 Increased shRNA abundance (Z-score > 2) GR00366-A-168 10.15 NDUFA10
15 Increased shRNA abundance (Z-score > 2) GR00366-A-176 10.15 NDUFA10
16 Increased shRNA abundance (Z-score > 2) GR00366-A-177 10.15 NDUFS7 NDUFA2
17 Increased shRNA abundance (Z-score > 2) GR00366-A-183 10.15 NDUFA10
18 Increased shRNA abundance (Z-score > 2) GR00366-A-54 10.15 BCS1L
19 Increased shRNA abundance (Z-score > 2) GR00366-A-57 10.15 NDUFS7 NDUFA9 NDUFA10 NDUFA2
20 Increased shRNA abundance (Z-score > 2) GR00366-A-63 10.15 NDUFA10 BCS1L
21 Increased shRNA abundance (Z-score > 2) GR00366-A-73 10.15 NDUFA9
22 Increased shRNA abundance (Z-score > 2) GR00366-A-76 10.15 NDUFA10
23 Increased shRNA abundance (Z-score > 2) GR00366-A-81 10.15 NDUFA9
24 Increased shRNA abundance (Z-score > 2) GR00366-A-85 10.15 NDUFA2
25 Increased shRNA abundance (Z-score > 2) GR00366-A-9 10.15 NDUFA2
26 Increased shRNA abundance (Z-score > 2) GR00366-A-96 10.15 COX10
27 Decreased shRNA abundance GR00297-A 9.43 NDUFS7 NDUFS8 SDHA NDUFS3 COX10 NDUFA10

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 1406-66-2 14986
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 Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome Enrolling by invitation NCT02352896 Phase 2 EPI-743
6 A Long-term Extension of Study RP103-MITO-001 (NCT02023866) to Assess Cysteamine Bitartrate Delayed-release Capsules (RP103) in Children With Inherited Mitochondrial Disease Terminated NCT02473445 Phase 2 Cysteamine Bitartrate
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) 29
2 Leigh Syndrome 29 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 29
4 Leigh Syndrome (mtdna Mutation) 29
5 Leigh Syndrome Due to Mitochondrial Complex Iii Deficiency 29

Anatomical Context for Leigh Syndrome

MalaCards organs/tissues related to Leigh Syndrome:

41
Cerebellum, Spinal Cord, Thalamus, Kidney, Eye, Brain, Heart

Publications for Leigh Syndrome

Articles related to Leigh Syndrome:

(show top 50) (show all 244)
# Title Authors Year
1
Novel insights into the functional metabolic impact of an apparent de novo m.8993T>G variant in the MT-ATP6 gene associated with maternally inherited form of Leigh Syndrome. ( 29602698 )
2018
2
Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome. ( 29625026 )
2018
3
Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family. ( 29512743 )
2018
4
Leigh syndrome with spinal cord involvement due to a hemizygous NDUFA1 mutation. ( 29506883 )
2018
5
Perioperative risk assessment for successful kidney transplant in leigh syndrome: a case report. ( 29390978 )
2018
6
Cytochrome C oxydase deficiency: SURF1 gene investigation in patients with Leigh syndrome. ( 29481804 )
2018
7
SURF1 mutations in Chinese patients with Leigh syndrome: Novel mutations, mutation spectrum, and the functional consequences. ( 29933018 )
2018
8
Spinal cord involvement in Leigh syndrome. ( 29739643 )
2018
9
Anesthetic Management in Pediatric Patient for Percutaneous Endoscopic Gastrostomy with Mitochondrial Myopathy: Leigh Syndrome. ( 29628597 )
2018
10
The cerebellum is a common site of affection in Leigh syndrome. ( 28963669 )
2018
11
Mito-Nuclear Interactions Affecting Lifespan and Neurodegeneration in a <i>Drosophila</i> Model of Leigh Syndrome. ( 29496745 )
2018
12
The Cerebellum Is a Common Site of Affection in Leigh Syndrome. ( 29056245 )
2018
13
Mutations in SURF1 are important genetic causes of Leigh syndrome in Slovak patients. ( 29715184 )
2018
14
A case report on a novel MT-ATP6 gene variation in atypical mitochondrial Leigh syndrome associated with bilateral basal ganglia calcifications. ( 29929013 )
2018
15
Leigh syndrome in individuals bearing m.9185T&amp;gt;C MTATP6 variant. Is hyperventilation a factor which starts its development? ( 29116603 )
2018
16
Correction for Ferrari et al., Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome. ( 29382743 )
2018
17
Phenotype-genotype correlations in Leigh syndrome: new insights from a multicentre study of 96 patients. ( 29101127 )
2018
18
Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome. ( 28777931 )
2017
19
Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome. ( 28483998 )
2017
20
Orbital rhabdomyosarcoma in a child with Leigh syndrome. ( 29274371 )
2017
21
Schizophrenia-like symptoms in a patient with Leigh syndrome. ( 28262162 )
2017
22
Why does Leigh syndrome respond to immunotherapy? ( 28649511 )
2017
23
Involvement of Cerebellum in Leigh Syndrome: Case Report and Review of the Literature. ( 28739363 )
2017
24
Loss of Mitochondrial Ndufs4 in Striatal Medium Spiny Neurons Mediates Progressive Motor Impairment in a Mouse Model of Leigh Syndrome. ( 28883788 )
2017
25
Widening the Heterogeneity of Leigh Syndrome: Clinical, Biochemical, and Neuroradiologic Features in a Patient Harboring a NDUFA10 Mutation. ( 28247337 )
2017
26
NDUFAF4 variants are associated with Leigh syndrome and cause a specific mitochondrial complex I assembly defect. ( 28853723 )
2017
27
Novel LRPPRC Mutation in a Boy With Mild Leigh Syndrome, French-Canadian Type Outside of QuAcbec. ( 29152527 )
2017
28
NDUFS4-related Leigh syndrome in Hutterites. ( 28371352 )
2017
29
Defective mitochondrial RNA processing due to PNPT1 variants causes Leigh syndrome. ( 28645153 )
2017
30
Modulation of mitochondrial dysfunction-related oxidative stress in fibroblasts of patients with Leigh syndrome by inhibition of prooxidative p66Shc pathway. ( 28739512 )
2017
31
Complete mtDNA sequencing reveals mutations m.9185T&amp;gt;C and m.13513G&amp;gt;A in three patients with Leigh syndrome. ( 29228836 )
2017
32
Management of Leigh Syndrome: current status and new insights. ( 28905387 )
2017
33
AAV9-based gene therapy partially ameliorates the clinical phenotype of a mouse model of Leigh syndrome. ( 28753212 )
2017
34
Response to correspondence of NDUFS4-related Leigh syndrome in Hutterites. ( 28371264 )
2017
35
Direct effects of mitochondrial dysfunction on poor bone health in Leigh syndrome. ( 28899781 )
2017
36
Novel mutation of ND4 gene identified by targeted next-generation sequencing in patient with Leigh syndrome. ( 27761019 )
2017
37
Correction for Ferrari et al., Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome. ( 28584118 )
2017
38
Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients. ( 28429146 )
2017
39
Traumatic brain injury is unlikely precipitating Leigh syndrome due to the GJB2 mutation c.35delG. ( 29201956 )
2017
40
Bioenergetic Impairment in Congenital Muscular Dystrophy Type 1A and Leigh Syndrome Muscle Cells. ( 28367954 )
2017
41
Head Trauma as a Precipitating Factor for Late-onset Leigh Syndrome: a Case Report. ( 28286850 )
2017
42
Is vatiquinone truly beneficial for Leigh syndrome? ( 29054334 )
2017
43
Fatigable ptosis as an initial presentation of adult-onset Leigh syndrome. ( 29038134 )
2017
44
Do lesional perfusion abnormalities on arterial spin labeling truly contribute to the diagnosis of Leigh syndrome? ( 27826676 )
2017
45
Japanese Leigh syndrome case treated with EPI-743. ( 28916229 )
2017
46
Premature Ovarian Failure in French Canadian Leigh Syndrome. ( 28284481 )
2017
47
Leigh Syndrome in Childhood: Neurologic Progression and Functional Outcome. ( 27074294 )
2016
48
SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome. ( 27390132 )
2016
49
Affection of the frontal lobe in Leigh syndrome due to the m.8993T&amp;gt;G mutation. ( 27209570 )
2016
50
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

Variations for Leigh Syndrome

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

75 (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 1085)
# Gene Variation Type Significance SNP ID Assembly Location
1 NDUFAF6 NM_152416.3(NDUFAF6): c.296A> G (p.Gln99Arg) single nucleotide variant Pathogenic rs137853184 GRCh37 Chromosome 8, 96044321: 96044321
2 NDUFAF6 NM_152416.3(NDUFAF6): c.296A> G (p.Gln99Arg) single nucleotide variant Pathogenic rs137853184 GRCh38 Chromosome 8, 95032093: 95032093
3 NDUFS3 NM_004551.2(NDUFS3): c.434C> T (p.Thr145Ile) single nucleotide variant Pathogenic rs28939714 GRCh37 Chromosome 11, 47603692: 47603692
4 NDUFS3 NM_004551.2(NDUFS3): c.434C> T (p.Thr145Ile) single nucleotide variant Pathogenic rs28939714 GRCh38 Chromosome 11, 47582140: 47582140
5 NDUFS3 NM_004551.2(NDUFS3): c.595C> T (p.Arg199Trp) single nucleotide variant Pathogenic rs104894270 GRCh37 Chromosome 11, 47603988: 47603988
6 NDUFS3 NM_004551.2(NDUFS3): c.595C> T (p.Arg199Trp) single nucleotide variant Pathogenic rs104894270 GRCh38 Chromosome 11, 47582436: 47582436
7 BCS1L NM_004328.4(BCS1L): c.296C> T (p.Pro99Leu) single nucleotide variant Pathogenic rs121908572 GRCh37 Chromosome 2, 219526006: 219526006
8 BCS1L NM_004328.4(BCS1L): c.296C> T (p.Pro99Leu) single nucleotide variant Pathogenic rs121908572 GRCh38 Chromosome 2, 218661283: 218661283
9 COX15 NM_004376.6(COX15): c.649C> T (p.Arg217Trp) single nucleotide variant Pathogenic rs28939711 GRCh37 Chromosome 10, 101483814: 101483814
10 COX15 NM_004376.6(COX15): c.649C> T (p.Arg217Trp) single nucleotide variant Pathogenic rs28939711 GRCh38 Chromosome 10, 99724057: 99724057
11 NDUFS4 NM_002495.3(NDUFS4): c.316C> T (p.Arg106Ter) single nucleotide variant Pathogenic rs104893898 GRCh37 Chromosome 5, 52942201: 52942201
12 NDUFS4 NM_002495.3(NDUFS4): c.316C> T (p.Arg106Ter) single nucleotide variant Pathogenic rs104893898 GRCh38 Chromosome 5, 53646371: 53646371
13 NDUFS4 NDUFS4, IVS1AS, G-A, -1 single nucleotide variant Pathogenic
14 NDUFA2 NDUFA2, IVS2DS, G-A, +5 single nucleotide variant Pathogenic
15 COX10 NM_001303.3(COX10): c.1007A> T (p.Asp336Val) single nucleotide variant Pathogenic rs104894557 GRCh37 Chromosome 17, 14110205: 14110205
16 COX10 NM_001303.3(COX10): c.1007A> T (p.Asp336Val) single nucleotide variant Pathogenic rs104894557 GRCh38 Chromosome 17, 14206888: 14206888
17 COX10 NM_001303.3(COX10): c.1007A> G (p.Asp336Gly) single nucleotide variant Pathogenic rs104894557 GRCh37 Chromosome 17, 14110205: 14110205
18 COX10 NM_001303.3(COX10): c.1007A> G (p.Asp336Gly) single nucleotide variant Pathogenic rs104894557 GRCh38 Chromosome 17, 14206888: 14206888
19 COX10 NM_001303.3(COX10): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs387906383 GRCh37 Chromosome 17, 13972924: 13972924
20 COX10 NM_001303.3(COX10): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs387906383 GRCh38 Chromosome 17, 14069607: 14069607
21 NDUFS7 NM_024407.4(NDUFS7): c.364G> A (p.Val122Met) single nucleotide variant Pathogenic rs104894705 GRCh37 Chromosome 19, 1391005: 1391005
22 NDUFS7 NM_024407.4(NDUFS7): c.364G> A (p.Val122Met) single nucleotide variant Pathogenic rs104894705 GRCh38 Chromosome 19, 1391006: 1391006
23 NDUFS7 NM_024407.4(NDUFS7): c.434G> A (p.Arg145His) single nucleotide variant Pathogenic rs121434479 GRCh37 Chromosome 19, 1391143: 1391143
24 NDUFS7 NM_024407.4(NDUFS7): c.434G> A (p.Arg145His) single nucleotide variant Pathogenic rs121434479 GRCh38 Chromosome 19, 1391144: 1391144
25 NDUFS7 NDUFS7, IVS1AS, C-G, -1167 single nucleotide variant Pathogenic
26 MT-TV m.1624C> T single nucleotide variant Pathogenic rs199476144 GRCh37 Chromosome MT, 1624: 1624
27 MT-TV m.1624C> T single nucleotide variant Pathogenic rs199476144 GRCh38 Chromosome MT, 1624: 1624
28 MT-TW m.5537_5538insT insertion Pathogenic rs199474672 GRCh37 Chromosome MT, 5537: 5538
29 MT-TW m.5537_5538insT insertion Pathogenic rs199474672 GRCh38 Chromosome MT, 5537: 5538
30 MT-TK m.8363G> A single nucleotide variant Pathogenic rs118192100 GRCh37 Chromosome MT, 8363: 8363
31 MT-TK m.8363G> A single nucleotide variant Pathogenic rs118192100 GRCh38 Chromosome MT, 8363: 8363
32 MT-TL1 m.3243A> G single nucleotide variant Pathogenic rs199474657 GRCh37 Chromosome MT, 3243: 3243
33 MT-TL1 m.3243A> G single nucleotide variant Pathogenic rs199474657 GRCh38 Chromosome MT, 3243: 3243
34 MT-ATP6 m.8993T> G single nucleotide variant Pathogenic rs199476133 GRCh37 Chromosome MT, 8993: 8993
35 MT-ATP6 m.8993T> G single nucleotide variant Pathogenic rs199476133 GRCh38 Chromosome MT, 8993: 8993
36 MT-ATP6 m.8993T> C single nucleotide variant Pathogenic rs199476133 GRCh37 Chromosome MT, 8993: 8993
37 MT-ATP6 m.8993T> C single nucleotide variant Pathogenic rs199476133 GRCh38 Chromosome MT, 8993: 8993
38 MT-ATP6 m.9176T> C single nucleotide variant Pathogenic rs199476135 GRCh37 Chromosome MT, 9176: 9176
39 MT-ATP6 m.9176T> C single nucleotide variant Pathogenic rs199476135 GRCh38 Chromosome MT, 9176: 9176
40 MT-ATP6 m.8851T> C single nucleotide variant Pathogenic rs199476136 GRCh37 Chromosome MT, 8851: 8851
41 MT-ATP6 m.8851T> C single nucleotide variant Pathogenic rs199476136 GRCh38 Chromosome MT, 8851: 8851
42 MT-ATP6 m.9185T> C single nucleotide variant Pathogenic rs199476138 GRCh37 Chromosome MT, 9185: 9185
43 MT-ATP6 m.9185T> C single nucleotide variant Pathogenic rs199476138 GRCh38 Chromosome MT, 9185: 9185
44 MT-ATP6 m.9176T> G single nucleotide variant Pathogenic rs199476135 GRCh37 Chromosome MT, 9176: 9176
45 MT-ATP6 m.9176T> G single nucleotide variant Pathogenic rs199476135 GRCh38 Chromosome MT, 9176: 9176
46 MT-CO3 m.9537dupC duplication Pathogenic rs267606614 GRCh37 Chromosome MT, 9537: 9537
47 MT-CO3 m.9537dupC duplication Pathogenic rs267606614 GRCh38 Chromosome MT, 9537: 9537
48 MT-ND6 NC_012920.1: m.14484T> C single nucleotide variant Pathogenic rs199476104 GRCh37 Chromosome MT, 14484: 14484
49 MT-ND6 NC_012920.1: m.14484T> C single nucleotide variant Pathogenic rs199476104 GRCh38 Chromosome MT, 14484: 14484
50 MT-ND6 m.14459G> A single nucleotide variant Pathogenic rs199476105 GRCh37 Chromosome MT, 14459: 14459

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:

37
# 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:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 mitochondrial membrane GO:0031966 9.97 COX10 COX15 MT-ND1 MT-ND3 MT-ND4 MT-ND6
2 mitochondrial matrix GO:0005759 9.88 NDUFA10 NDUFA9 NDUFS3 NDUFS7 NDUFS8
3 respiratory chain GO:0070469 9.77 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFA10
4 myelin sheath GO:0043209 9.69 NDUFA10 NDUFS3 SDHA
5 mitochondrial respiratory chain GO:0005746 9.49 COX15 SURF1
6 respiratory chain complex I GO:0045271 9.46 MT-ND4 NDUFS4
7 cytochrome complex GO:0070069 9.43 COX10 COX15
8 NADH dehydrogenase complex GO:0030964 9.4 MT-ND3 NDUFA12
9 mitochondrial respiratory chain complex I GO:0005747 9.4 MT-ND1 MT-ND3 MT-ND4 MT-ND5 NDUFA10 NDUFA12
10 membrane GO:0016020 10.3 BCS1L COX10 COX15 MT-ATP6 MT-ND1 MT-ND3
11 mitochondrion GO:0005739 10.21 BCS1L COX10 COX15 MT-ND1 MT-ND3 MT-ND4
12 mitochondrial inner membrane GO:0005743 10.11 BCS1L COX10 COX15 MT-ATP6 MT-ND1 MT-ND3

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

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 mitochondrial respiratory chain complex I assembly GO:0032981 9.83 BCS1L MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
2 response to oxidative stress GO:0006979 9.71 MT-ND3 NDUFA12 NDUFS8
3 electron transport chain GO:0022900 9.71 NDUFA12 NDUFS4 SDHA SURF1
4 proton transmembrane transport GO:1902600 9.67 COX10 COX15 SURF1
5 cellular respiration GO:0045333 9.65 COX10 COX15 MT-ND1 NDUFS3 NDUFS4
6 aerobic respiration GO:0009060 9.62 COX10 MT-ND4 NDUFS7 SURF1
7 ATP biosynthetic process GO:0006754 9.56 MT-ATP6 SURF1
8 mitochondrial electron transport, cytochrome c to oxygen GO:0006123 9.55 COX10 COX15
9 respiratory chain complex IV assembly GO:0008535 9.54 COX10 COX15 SURF1
10 heme biosynthetic process GO:0006783 9.52 COX10 COX15
11 mitochondrial respiratory chain complex IV assembly GO:0033617 9.51 BCS1L SURF1
12 ATP synthesis coupled electron transport GO:0042773 9.48 MT-ND4 MT-ND5
13 electron transport coupled proton transport GO:0015990 9.46 MT-ND4 NDUFS7
14 mitochondrial electron transport, NADH to ubiquinone GO:0006120 9.44 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFA10
15 heme a biosynthetic process GO:0006784 9.43 COX10 COX15
16 oxidation-reduction process GO:0055114 10.06 COX15 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6

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

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.81 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFS3
2 NADH dehydrogenase (ubiquinone) activity GO:0008137 9.77 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFA10
3 electron transfer activity GO:0009055 9.54 NDUFA12 NDUFS3 SDHA
4 cytochrome-c oxidase activity GO:0004129 9.5 COX10 COX15 SURF1
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 9.17 MT-ND1 MT-ND4 MT-ND5 NDUFA9 NDUFS3 NDUFS7

Sources for Leigh Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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