LS
MCID: LGH007
MIFTS: 69

Leigh Syndrome (LS)

Categories: Cardiovascular diseases, Eye diseases, Genetic diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare 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
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
Syndrome, Leigh 40
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 leigh syndrome with leukodystrophy and mitochondrial complex iv deficiency, and has symptoms including seizures, ataxia 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 spinal cord, cerebellum and thalamus, and related phenotypes are ptosis and nystagmus

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 : 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.

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.

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.

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 161)
# Related Disease Score Top Affiliating Genes
1 leigh syndrome with leukodystrophy 33.5 COX15 FOXRED1 NDUFA10 NDUFA12 NDUFA2 NDUFA9
2 mitochondrial complex iv deficiency 32.9 COX10 COX15 MT-ND4 SURF1
3 mitochondrial complex i deficiency 32.9 FOXRED1 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
4 striatonigral degeneration, infantile, mitochondrial 32.1 MT-ATP6 MT-ND3 MT-ND4
5 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 32.1 MT-ATP6 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
6 striatonigral degeneration, infantile 32.1 MT-ATP6 MT-ND3 MT-ND4
7 neuropathy 30.9 MT-ATP6 MT-ND1 MT-ND4 MT-ND5 MT-ND6
8 dystonia 30.8 MT-ND1 MT-ND3 MT-ND4 MT-ND6
9 mitochondrial metabolism disease 30.6 COX10 COX15 FOXRED1 MT-ATP6 MT-ND3 MT-ND4
10 optic nerve disease 30.5 MT-ATP6 MT-ND1 MT-ND4 MT-ND5 MT-ND6
11 mitochondrial myopathy 30.3 MT-ATP6 MT-ND1 MT-ND4 MT-ND5 MT-ND6
12 lactic acidosis 30.3 MT-ATP6 MT-ND1 MT-ND4 MT-ND5 MT-ND6
13 ataxia and polyneuropathy, adult-onset 30.3 MT-ATP6 MT-ND3 MT-ND4
14 leber hereditary optic neuropathy 30.2 FOXRED1 MT-ATP6 MT-ND1 MT-ND3 MT-ND4 MT-ND5
15 leigh syndrome, french canadian type 12.6
16 mitochondrial dna-associated leigh syndrome 12.5
17 nuclear gene-encoded leigh syndrome 12.3
18 mitochondrial dna-associated leigh syndrome and narp 12.1
19 leigh syndrome with nephrotic syndrome 12.0
20 lichen sclerosus et atrophicus 11.6
21 lichen sclerosus 11.6
22 pyruvate carboxylase deficiency 11.4
23 balanitis xerotica obliterans 11.2
24 coenzyme q10 deficiency, primary, 1 11.1
25 3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome 11.1
26 cholestasis, benign recurrent intrahepatic, 2 11.1
27 necrotizing encephalomyelopathy, subacute, of leigh, adult 11.0
28 larsen syndrome 11.0
29 desbuquois dysplasia 1 11.0
30 legius syndrome 11.0
31 3-hydroxyisobutyryl-coa hydrolase deficiency 11.0
32 mitochondrial complex ii deficiency 11.0
33 coenzyme q10 deficiency, primary, 3 11.0
34 coenzyme q10 deficiency, primary, 5 11.0
35 combined oxidative phosphorylation deficiency 15 11.0
36 mitochondrial complex iii deficiency, nuclear type 2 11.0
37 combined oxidative phosphorylation deficiency 32 11.0
38 leber optic atrophy and dystonia 10.4 MT-ND1 MT-ND3 MT-ND4 MT-ND6
39 leber optic atrophy 10.4 MT-ATP6 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
40 familial colorectal cancer 10.4 MT-ATP6 MT-ND3 MT-ND4 MT-ND5 MT-ND6
41 deafness, nonsyndromic sensorineural, mitochondrial 10.4 MT-ATP6 MT-ND1 MT-ND4 MT-ND5
42 kearns-sayre syndrome 10.4 MT-ATP6 MT-ND1 MT-ND4 MT-ND5 MT-ND6 SDHA
43 myopathy, lactic acidosis, and sideroblastic anemia 3 10.4 MT-ATP6 MT-ND3 MT-ND4
44 myopathy, lactic acidosis, and sideroblastic anemia 10.4 MT-ATP6 MT-ND3 MT-ND4
45 mitochondrial encephalomyopathy 10.4 MT-ATP6 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
46 cranial nerve disease 10.4 MT-ND1 MT-ND4 MT-ND5 MT-ND6
47 dysphagia 10.4 NDUFA10 NDUFA12 NDUFA9
48 lymphosarcoma 10.4
49 sparganosis 10.4 MT-ND3 MT-ND4
50 comedo carcinoma 10.4 NDUFS3 NDUFS4

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 ophthalmoplegia 32 HP:0000602
25 generalized hypotonia 32 HP:0001290
26 progressive spastic paraplegia 32 frequent (33%) HP:0007020
27 abnormal pattern of respiration 32 HP:0002793
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 cns demyelination 32 HP:0007305
34 hepatocellular necrosis 32 HP:0001404
35 progressive ophthalmoplegia 32 frequent (33%) HP:0007650

UMLS symptoms related to Leigh Syndrome:


seizures, ataxia, ophthalmoplegia, muscle spasticity

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

26 (show all 23)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-102 9.8 NDUFS7
2 Increased shRNA abundance (Z-score > 2) GR00366-A-107 9.8 NDUFA10
3 Increased shRNA abundance (Z-score > 2) GR00366-A-11 9.8 NDUFA2
4 Increased shRNA abundance (Z-score > 2) GR00366-A-114 9.8 NDUFA2
5 Increased shRNA abundance (Z-score > 2) GR00366-A-115 9.8 NDUFA10 NDUFA9 NDUFS7
6 Increased shRNA abundance (Z-score > 2) GR00366-A-120 9.8 NDUFA10 NDUFS7
7 Increased shRNA abundance (Z-score > 2) GR00366-A-129 9.8 NDUFA9
8 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.8 NDUFA2
9 Increased shRNA abundance (Z-score > 2) GR00366-A-16 9.8 NDUFS7
10 Increased shRNA abundance (Z-score > 2) GR00366-A-162 9.8 NDUFA2
11 Increased shRNA abundance (Z-score > 2) GR00366-A-166 9.8 NDUFA10 NDUFA9
12 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.8 NDUFA10
13 Increased shRNA abundance (Z-score > 2) GR00366-A-176 9.8 NDUFA10
14 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.8 NDUFA2 NDUFS7
15 Increased shRNA abundance (Z-score > 2) GR00366-A-183 9.8 NDUFA10
16 Increased shRNA abundance (Z-score > 2) GR00366-A-57 9.8 NDUFA10 NDUFA2 NDUFA9 NDUFS7
17 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.8 NDUFA10
18 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.8 NDUFA9
19 Increased shRNA abundance (Z-score > 2) GR00366-A-76 9.8 NDUFA10
20 Increased shRNA abundance (Z-score > 2) GR00366-A-81 9.8 NDUFA9
21 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.8 NDUFA2
22 Increased shRNA abundance (Z-score > 2) GR00366-A-9 9.8 NDUFA2
23 Decreased shRNA abundance GR00297-A 9.43 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 Phase 2 1406-66-2 14986
3
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
4 Tocotrienol Investigational Phase 2 6829-55-6
5 Micronutrients Phase 2
6 Trace Elements Phase 2
7 Ubiquinone Phase 2
8 Tocopherols Phase 2
9 Tocotrienols Phase 2
10 Tocotrienol, alpha Phase 2

Interventional clinical trials:

(show all 12)
# Name Status NCT ID Phase Drugs
1 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
2 Open-Label, Dose-Escalating Study Assessing Safety, Tolerability, Efficacy, of RP103 in Mitochondrial Disease Completed NCT02023866 Phase 2 Cysteamine Bitartrate
3 The KHENERGY Study Completed NCT02909400 Phase 2 KH176;placebo
4 Long-Term Safety and Efficacy Evaluation of EPI-743 in Children With Leigh Syndrome Active, not recruiting NCT02352896 Phase 2 EPI-743
5 EPI-743 for Mitochondrial Respiratory Chain Diseases Active, not recruiting NCT01370447 Phase 2 EPI-743
6 ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome Not yet recruiting NCT03747328 Phase 2 ABI-009
7 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
8 A Dose-escalating Clinical Trial With KH176 Completed NCT02544217 Phase 1 KH176;placebo
9 The Leigh Syndrome Registry Recruiting NCT03137355
10 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168
11 North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC) Recruiting NCT01694940
12 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
Spinal Cord, Cerebellum, Thalamus, Kidney, Brain, Eye, Heart

Publications for Leigh Syndrome

Articles related to Leigh Syndrome:

(show top 50) (show all 399)
# Title Authors Year
1
Osteoblastic differentiation improved by bezafibrate-induced mitochondrial biogenesis in deciduous tooth-derived pulp stem cells from a child with Leigh syndrome. ( 30533535 )
2019
2
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
3
Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome. ( 29625026 )
2018
4
Leigh syndrome T8993C mitochondrial DNA mutation: Heteroplasmy and the first clinical presentation in a Vietnamese family. ( 29512743 )
2018
5
Leigh syndrome with spinal cord involvement due to a hemizygous NDUFA1 mutation. ( 29506883 )
2018
6
Perioperative risk assessment for successful kidney transplant in leigh syndrome: a case report. ( 29390978 )
2018
7
Cytochrome C oxydase deficiency: SURF1 gene investigation in patients with Leigh syndrome. ( 29481804 )
2018
8
SURF1 mutations in Chinese patients with Leigh syndrome: Novel mutations, mutation spectrum, and the functional consequences. ( 29933018 )
2018
9
Spinal cord involvement in Leigh syndrome. ( 29739643 )
2018
10
Anesthetic Management in Pediatric Patient for Percutaneous Endoscopic Gastrostomy with Mitochondrial Myopathy: Leigh Syndrome. ( 29628597 )
2018
11
The cerebellum is a common site of affection in Leigh syndrome. ( 28963669 )
2018
12
Mito-Nuclear Interactions Affecting Lifespan and Neurodegeneration in a <i>Drosophila</i> Model of Leigh Syndrome. ( 29496745 )
2018
13
The Cerebellum Is a Common Site of Affection in Leigh Syndrome. ( 29056245 )
2018
14
Mutations in SURF1 are important genetic causes of Leigh syndrome in Slovak patients. ( 29715184 )
2018
15
A case report on a novel MT-ATP6 gene variation in atypical mitochondrial Leigh syndrome associated with bilateral basal ganglia calcifications. ( 29929013 )
2018
16
Leigh syndrome in individuals bearing m.9185T&amp;gt;C MTATP6 variant. Is hyperventilation a factor which starts its development? ( 29116603 )
2018
17
Overlapping Leigh Syndrome/Myoclonic Epilepsy With Ragged Red Fibres in an Adolescent Patient With a Mitochondrial DNA A8344G Mutation. ( 30271374 )
2018
18
A case of prenatal chronic intestinal pseudo-obstruction associated with Leigh syndrome. ( 30147885 )
2018
19
Phenotype-genotype correlations in Leigh syndrome: new insights from a multicentre study of 96 patients. ( 29101127 )
2018
20
Correction for Ferrari et al., Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome. ( 29382743 )
2018
21
Vaccination triggering onset of m.8993T > G associated Leigh syndrome. ( 30023303 )
2018
22
Phenotypic spectrum of maternally inherited Leigh Syndrome associated with the m.8993T>G variant. ( 30023306 )
2018
23
Next generation sequencing technologies for a successful diagnosis in a cold case of Leigh syndrome. ( 30029642 )
2018
24
Late-Onset Leigh Syndrome due to NDUFV1 Mutation in a 10-Year-Old Boy Initially Presenting with Ataxia. ( 30090137 )
2018
25
Mitochondrial DNA mutations in late-onset Leigh syndrome. ( 30128709 )
2018
26
Adult-onset Leigh syndrome with central fever and peripheral neuropathy due to mitochondrial 9176T>C mutation. ( 30136164 )
2018
27
A Novel NDUFS3 mutation in a Chinese patient with severe Leigh syndrome. ( 30140060 )
2018
28
Three-Dimensional Analysis of Mitochondrial Crista Ultrastructure in a Patient with Leigh Syndrome by In Situ Cryoelectron Tomography. ( 30240627 )
2018
29
Correction: A novel NDUFS3 mutation in a Chinese patient with severe Leigh syndrome. ( 30266949 )
2018
30
LEIGH SYNDROME: A CASE REPORT WITH A MITOCHONDRIAL DNA MUTATION. ( 30379275 )
2018
31
FOXRED1 silencing in mice: a possible animal model for Leigh syndrome. ( 30392038 )
2018
32
Clinical, Neuroimaging, and Pathological Analyses of 13 Chinese Leigh Syndrome Patients with Mitochondrial DNA Mutations. ( 30425197 )
2018
33
Ophthalmic manifestations in patients with Leigh syndrome, French Canadian type. ( 30426811 )
2018
34
Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD. ( 30429455 )
2018
35
Reply to the Letter, "Leigh syndrome with spinal cord involvement due to a hemizygous NDUFA1 mutation". ( 30458972 )
2018
36
Impaired Hypoxic Pulmonary Vasoconstriction in a Mouse Model of Leigh Syndrome. ( 30520688 )
2018
37
Silencing of FOXRED1 in C57b1/6 mice does not generate an appropriate animal model of Leigh syndrome. ( 30523580 )
2018
38
Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome. ( 28777931 )
2017
39
Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome. ( 28483998 )
2017
40
Orbital rhabdomyosarcoma in a child with Leigh syndrome. ( 29274371 )
2017
41
Schizophrenia-like symptoms in a patient with Leigh syndrome. ( 28262162 )
2017
42
Why does Leigh syndrome respond to immunotherapy? ( 28649511 )
2017
43
Involvement of Cerebellum in Leigh Syndrome: Case Report and Review of the Literature. ( 28739363 )
2017
44
Loss of Mitochondrial Ndufs4 in Striatal Medium Spiny Neurons Mediates Progressive Motor Impairment in a Mouse Model of Leigh Syndrome. ( 28883788 )
2017
45
Widening the Heterogeneity of Leigh Syndrome: Clinical, Biochemical, and Neuroradiologic Features in a Patient Harboring a NDUFA10 Mutation. ( 28247337 )
2017
46
NDUFAF4 variants are associated with Leigh syndrome and cause a specific mitochondrial complex I assembly defect. ( 28853723 )
2017
47
Novel LRPPRC Mutation in a Boy With Mild Leigh Syndrome, French-Canadian Type Outside of QuAcbec. ( 29152527 )
2017
48
NDUFS4-related Leigh syndrome in Hutterites. ( 28371352 )
2017
49
Defective mitochondrial RNA processing due to PNPT1 variants causes Leigh syndrome. ( 28645153 )
2017
50
Modulation of mitochondrial dysfunction-related oxidative stress in fibroblasts of patients with Leigh syndrome by inhibition of prooxidative p66Shc pathway. ( 28739512 )
2017

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 1268)
# 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 NDUFAF2 NM_174889.4(NDUFAF2): c.139C> T (p.Arg47Ter) single nucleotide variant Pathogenic rs137852863 GRCh37 Chromosome 5, 60368963: 60368963
4 NDUFAF2 NM_174889.4(NDUFAF2): c.139C> T (p.Arg47Ter) single nucleotide variant Pathogenic rs137852863 GRCh38 Chromosome 5, 61073136: 61073136
5 NDUFS3 NM_004551.2(NDUFS3): c.434C> T (p.Thr145Ile) single nucleotide variant Pathogenic rs28939714 GRCh37 Chromosome 11, 47603692: 47603692
6 NDUFS3 NM_004551.2(NDUFS3): c.434C> T (p.Thr145Ile) single nucleotide variant Pathogenic rs28939714 GRCh38 Chromosome 11, 47582140: 47582140
7 NDUFS3 NM_004551.2(NDUFS3): c.595C> T (p.Arg199Trp) single nucleotide variant Pathogenic rs104894270 GRCh37 Chromosome 11, 47603988: 47603988
8 NDUFS3 NM_004551.2(NDUFS3): c.595C> T (p.Arg199Trp) single nucleotide variant Pathogenic rs104894270 GRCh38 Chromosome 11, 47582436: 47582436
9 BCS1L NM_004328.4(BCS1L): c.296C> T (p.Pro99Leu) single nucleotide variant Likely pathogenic rs121908572 GRCh37 Chromosome 2, 219526006: 219526006
10 BCS1L NM_004328.4(BCS1L): c.296C> T (p.Pro99Leu) single nucleotide variant Likely pathogenic rs121908572 GRCh38 Chromosome 2, 218661283: 218661283
11 COX15 NM_004376.6(COX15): c.649C> T (p.Arg217Trp) single nucleotide variant Pathogenic rs28939711 GRCh37 Chromosome 10, 101483814: 101483814
12 COX15 NM_004376.6(COX15): c.649C> T (p.Arg217Trp) single nucleotide variant Pathogenic rs28939711 GRCh38 Chromosome 10, 99724057: 99724057
13 NDUFS4 NM_002495.3(NDUFS4): c.316C> T (p.Arg106Ter) single nucleotide variant Pathogenic rs104893898 GRCh37 Chromosome 5, 52942201: 52942201
14 NDUFS4 NM_002495.3(NDUFS4): c.316C> T (p.Arg106Ter) single nucleotide variant Pathogenic rs104893898 GRCh38 Chromosome 5, 53646371: 53646371
15 NDUFA2 NM_002488.4(NDUFA2): c.208+5G> A single nucleotide variant Pathogenic GRCh38 Chromosome 5, 140647251: 140647251
16 NDUFA2 NM_002488.4(NDUFA2): c.208+5G> A single nucleotide variant Pathogenic GRCh37 Chromosome 5, 140026836: 140026836
17 COX10 NM_001303.3(COX10): c.1007A> T (p.Asp336Val) single nucleotide variant Pathogenic rs104894557 GRCh37 Chromosome 17, 14110205: 14110205
18 COX10 NM_001303.3(COX10): c.1007A> T (p.Asp336Val) single nucleotide variant Pathogenic rs104894557 GRCh38 Chromosome 17, 14206888: 14206888
19 COX10 NM_001303.3(COX10): c.1007A> G (p.Asp336Gly) single nucleotide variant Pathogenic rs104894557 GRCh37 Chromosome 17, 14110205: 14110205
20 COX10 NM_001303.3(COX10): c.1007A> G (p.Asp336Gly) single nucleotide variant Pathogenic rs104894557 GRCh38 Chromosome 17, 14206888: 14206888
21 COX10 NM_001303.3(COX10): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs387906383 GRCh37 Chromosome 17, 13972924: 13972924
22 COX10 NM_001303.3(COX10): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic rs387906383 GRCh38 Chromosome 17, 14069607: 14069607
23 NDUFS7 NM_024407.4(NDUFS7): c.364G> A (p.Val122Met) single nucleotide variant Pathogenic rs104894705 GRCh37 Chromosome 19, 1391005: 1391005
24 NDUFS7 NM_024407.4(NDUFS7): c.364G> A (p.Val122Met) single nucleotide variant Pathogenic rs104894705 GRCh38 Chromosome 19, 1391006: 1391006
25 NDUFS7 NM_024407.4(NDUFS7): c.434G> A (p.Arg145His) single nucleotide variant Pathogenic rs121434479 GRCh37 Chromosome 19, 1391143: 1391143
26 NDUFS7 NM_024407.4(NDUFS7): c.434G> A (p.Arg145His) single nucleotide variant Pathogenic rs121434479 GRCh38 Chromosome 19, 1391144: 1391144
27 NDUFS7 NM_024407.4(NDUFS7): c.17-1167C> G single nucleotide variant Pathogenic GRCh38 Chromosome 19, 1386644: 1386644
28 NDUFS7 NM_024407.4(NDUFS7): c.17-1167C> G single nucleotide variant Pathogenic GRCh37 Chromosome 19, 1386643: 1386643
29 MT-TV m.1624C> T single nucleotide variant Pathogenic rs199476144 GRCh37 Chromosome MT, 1624: 1624
30 MT-TV m.1624C> T single nucleotide variant Pathogenic rs199476144 GRCh38 Chromosome MT, 1624: 1624
31 MT-TW m.5537_5538insT insertion Pathogenic rs199474672 GRCh37 Chromosome MT, 5537: 5538
32 MT-TW m.5537_5538insT insertion Pathogenic rs199474672 GRCh38 Chromosome MT, 5537: 5538
33 MT-TK m.8344A> G single nucleotide variant Conflicting interpretations of pathogenicity rs118192098 GRCh37 Chromosome MT, 8344: 8344
34 MT-TK m.8344A> G single nucleotide variant Conflicting interpretations of pathogenicity rs118192098 GRCh38 Chromosome MT, 8344: 8344
35 MT-TK m.8363G> A single nucleotide variant Pathogenic rs118192100 GRCh37 Chromosome MT, 8363: 8363
36 MT-TK m.8363G> A single nucleotide variant Pathogenic rs118192100 GRCh38 Chromosome MT, 8363: 8363
37 MT-TL1 NC_012920.1: m.3243A> G single nucleotide variant Pathogenic rs199474657 GRCh37 Chromosome MT, 3243: 3243
38 MT-TL1 NC_012920.1: m.3243A> G single nucleotide variant Pathogenic rs199474657 GRCh38 Chromosome MT, 3243: 3243
39 MT-ATP6 m.8993T> G single nucleotide variant Pathogenic rs199476133 GRCh37 Chromosome MT, 8993: 8993
40 MT-ATP6 m.8993T> G single nucleotide variant Pathogenic rs199476133 GRCh38 Chromosome MT, 8993: 8993
41 MT-ATP6 m.8993T> C single nucleotide variant Pathogenic rs199476133 GRCh37 Chromosome MT, 8993: 8993
42 MT-ATP6 m.8993T> C single nucleotide variant Pathogenic rs199476133 GRCh38 Chromosome MT, 8993: 8993
43 MT-ATP6 m.9176T> C single nucleotide variant Pathogenic rs199476135 GRCh37 Chromosome MT, 9176: 9176
44 MT-ATP6 m.9176T> C single nucleotide variant Pathogenic rs199476135 GRCh38 Chromosome MT, 9176: 9176
45 MT-ATP6 m.8851T> C single nucleotide variant Pathogenic rs199476136 GRCh37 Chromosome MT, 8851: 8851
46 MT-ATP6 m.8851T> C single nucleotide variant Pathogenic rs199476136 GRCh38 Chromosome MT, 8851: 8851
47 MT-ATP6 m.9185T> C single nucleotide variant Pathogenic rs199476138 GRCh37 Chromosome MT, 9185: 9185
48 MT-ATP6 m.9185T> C single nucleotide variant Pathogenic rs199476138 GRCh38 Chromosome MT, 9185: 9185
49 MT-ATP6 m.9176T> G single nucleotide variant Pathogenic rs199476135 GRCh37 Chromosome MT, 9176: 9176
50 MT-ATP6 m.9176T> G single nucleotide variant Pathogenic rs199476135 GRCh38 Chromosome MT, 9176: 9176

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:

# 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 9.83 NDUFA10 NDUFA9 NDUFS3 NDUFS7 NDUFS8
3 respiratory chain GO:0070469 9.8 FOXRED1 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
4 myelin sheath GO:0043209 9.65 NDUFA10 NDUFS3 SDHA
5 mitochondrial respiratory chain GO:0005746 9.46 COX15 SURF1
6 mitochondrial respiratory chain complex I GO:0005747 9.44 FOXRED1 MT-ND1 MT-ND3 MT-ND4 MT-ND5 NDUFA10
7 cytochrome complex GO:0070069 9.4 COX10 COX15
8 membrane GO:0016020 10.3 COX10 COX15 FOXRED1 MT-ATP6 MT-ND1 MT-ND3
9 mitochondrial inner membrane GO:0005743 10.19 COX10 COX15 FOXRED1 MT-ATP6 MT-ND1 MT-ND3
10 mitochondrion GO:0005739 10.09 COX10 COX15 FOXRED1 MT-ND1 MT-ND3 MT-ND4

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

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 mitochondrial respiratory chain complex I assembly GO:0032981 9.83 FOXRED1 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
2 aerobic respiration GO:0009060 9.73 COX10 MT-ND1 MT-ND4 NDUFS7 NDUFS8 SURF1
3 response to oxidative stress GO:0006979 9.71 MT-ND3 NDUFA12 NDUFS8
4 electron transport chain GO:0022900 9.71 NDUFA12 NDUFS4 SDHA SURF1
5 proton transmembrane transport GO:1902600 9.69 COX10 COX15 SURF1
6 ATP biosynthetic process GO:0006754 9.55 MT-ATP6 SURF1
7 cellular respiration GO:0045333 9.54 COX10 COX15 NDUFS4
8 heme biosynthetic process GO:0006783 9.52 COX10 COX15
9 respiratory chain complex IV assembly GO:0008535 9.5 COX10 COX15 SURF1
10 mitochondrial electron transport, cytochrome c to oxygen GO:0006123 9.49 COX10 COX15
11 ATP synthesis coupled electron transport GO:0042773 9.48 MT-ND4 MT-ND5
12 electron transport coupled proton transport GO:0015990 9.46 MT-ND4 NDUFS7
13 heme a biosynthetic process GO:0006784 9.43 COX10 COX15
14 mitochondrial electron transport, NADH to ubiquinone GO:0006120 9.36 MT-ND1 MT-ND3 MT-ND4 MT-ND5 NDUFA10 NDUFA2
15 oxidation-reduction process GO:0055114 10.09 COX15 FOXRED1 MT-ND1 MT-ND3 MT-ND4 MT-ND5

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

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.85 FOXRED1 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
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
Content
Loading form....