MCID: LGH007
MIFTS: 69

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 54 12 50 24 24 24 24 25 71 29 29 29 52
Leigh Disease 12 50 24 25 71 42 14 69
Leigh Syndrome Due to Mitochondrial Complex I Deficiency 54 24 71 29
Leigh Syndrome Due to Cytochrome C Oxidase Deficiency 54 24 13
Leigh's Disease 50 25 51
Sne 50 24 71
Ls 50 24 71
Leigh Syndrome Due to Mitochondrial Complex Iii Deficiency 71 29
Leigh Syndrome Due to Mitochondrial Complex Ii Deficiency 71 29
Necrotizing Encephalopathy Infantile Subacute of Leigh 50 71
Infantile Subacute Necrotizing Encephalopathy 50 25
Subacute Necrotizing Encephalomyelopathy 12 25
Cardiomyopathy with Hypotonia Due to Cytochrome C Oxidase Deficiency 56
Maternally-Inherited Infantile Subacute Necrotizing Encephalopathy 56
Necrotizing Encephalopathy, Infantile, Subacute, of Leigh 24
Leigh Syndrome Due to Mitochondrial Complex Iv Deficiency 71
Leigh Syndrome Due to Mitochondrial Complex 1 Deficiency 54
Leigh Syndrome Due to Mitochondrial Complex V Deficiency 71
Necrotizing Encephalopathy, Infantile Subacute, of Leigh 69
Leigh Syndrome Due to Mitochondrial Cox4 Deficiency 54
Cardiomyopathy with Myopathy Due to Cox Deficiency 56
Juvenile Subacute Necrotizing Encephalomyelopathy 12
Encephalopathy, Subacute Necrotizing, Infantile 69
Encephalopathy, Subacute Necrotizing, Juvenile 69
Juvenile Subacute Necrotizing Encephalopathy 25
Infantile Necrotizing Encephalomyelopathy 12
Leigh Syndrome, Due to Cox Iv Deficiency 54
Subacute Necrotizing Encephalopathy 50
Maternally Inherited Leigh Syndrome 69
Maternally-Inherited Leigh Syndrome 56
Leigh's Necrotizing Encephalopathy 50
Maternally-Inherited Leigh Disease 56
Leigh Syndrome with Cardiomyopathy 56
Leigh Disease with Myopathy 56
Mils 56

Characteristics:

Orphanet epidemiological data:

56
maternally-inherited leigh syndrome
Inheritance: Mitochondrial inheritance; Age of onset: Childhood,Infancy;

OMIM:

54
Inheritance:
autosomal recessive
mitochondrial

Miscellaneous:
genetic heterogeneity (may be caused by mutation in nuclear-encoded or mitochondrial-encoded genes)
onset usually in infancy or early childhood
progressive disorder, usually with rapid, relentless course
clinical heterogeneity
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 : 51 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 complex i deficiency and leigh syndrome, french-canadian type, and has symptoms including failure to thrive, hypertrichosis and optic atrophy. An important gene associated with Leigh Syndrome is SURF1 (SURF1, Cytochrome C Oxidase Assembly Factor), and among its related pathways/superpathways are Metabolism and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. The drugs Cysteamine and Tocopherol have been mentioned in the context of this disorder. Affiliated tissues include cerebellum, spinal cord and thalamus, and related phenotype is Increased shRNA abundance (Z-score > 2).

NIH Rare Diseases : 50 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

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.

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.

OMIM : 54
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)

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

Related Diseases for Leigh Syndrome

Diseases in the Leigh Syndrome family:

Leigh-Like Syndrome

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

(show top 50) (show all 84)
id Related Disease Score Top Affiliating Genes
1 mitochondrial complex i deficiency 33.3 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFA10
2 leigh syndrome, french-canadian type 12.2
3 mitochondrial dna-associated leigh syndrome 12.2
4 nuclear gene-encoded leigh syndrome 12.1
5 mitochondrial dna-associated leigh syndrome and narp 12.0
6 x-linked leigh syndrome 11.8
7 leigh syndrome with leukodystrophy 11.7
8 leigh syndrome with nephrotic syndrome 11.7
9 lichen sclerosus 11.3
10 parkinson disease 6, early onset 11.0 MT-ND5 MT-ND6
11 hypokalemic periodic paralysis, type 2 11.0 COX15 SURF1
12 pyruvate carboxylase deficiency 11.0
13 mental retardation with spastic paraplegia 11.0 MT-ATP6 MT-ND4 MT-ND5 MT-ND6 SDHA
14 balanitis xerotica obliterans 11.0
15 mitochondrial neurogastrointestinal encephalopathy disease 11.0 MT-ATP6 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
16 leiner disease 11.0 MT-ND1 MT-ND3 MT-ND4 MT-ND6
17 nerve fibre bundle defect 11.0 NDUFS3 NDUFS4
18 androgen insensitivity 11.0 MT-ATP6 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
19 enchondromatosis dwarfism deafness 11.0 MT-ND1 MT-ND4 MT-ND5 MT-ND6
20 mitochondrial complex iv deficiency 11.0
21 cutaneous mastocytosis 11.0 MT-ATP6 MT-ND1 MT-ND4 MT-ND5 MT-ND6
22 pleomorphic carcinoma 11.0 MT-ND1 MT-ND4 MT-ND5 MT-ND6
23 myoclonic epilepsy associated with ragged-red fibers 11.0 MT-ATP6 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
24 mixed germ cell tumor of central nervous system 10.9 COX15 NDUFA10 NDUFA12 NDUFA2 NDUFA9 NDUFAF2
25 gastric leiomyoma 10.9 MT-ND3 MT-ND4
26 allergic contact dermatitis of eyelid 10.9 MT-ND1 MT-ND4 MT-ND5 MT-ND6
27 protoplasmic astrocytoma 10.9 COX15 MT-ATP6 MT-ND3 MT-ND4 MT-ND5 MT-ND6
28 chondroid chordoma 10.9 NDUFA12 NDUFA2
29 decubitus ulcer 10.9 MT-ATP6 MT-ND1 MT-ND4 MT-ND5 MT-ND6
30 cardiomyopathy and deafness due to trna lysine gene mutation 10.9 COX15 SURF1
31 coenzyme q10 deficiency, primary, 1 10.9
32 3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome 10.9
33 cholestasis, benign recurrent intrahepatic, 2 10.9
34 lmna-related emery-dreifuss muscular dystrophy, autosomal 10.9 NDUFS4 SURF1
35 reproductive system disease 10.8 MT-ATP6 MT-ND1
36 larsen syndrome 10.8
37 legius syndrome 10.8
38 extrapontine myelinolysis 10.7 MT-ND3 MT-ND5
39 combined oxidative phosphorylation deficiency 15 10.7
40 coenzyme q10 deficiency, primary, 5 10.7
41 combined oxidative phosphorylation deficiency 32 10.7
42 mitochondrial complex iii deficiency, nuclear type 2 10.7
43 striatonigral degeneration, infantile 10.7
44 3-hydroxyisobutryl-coa hydrolase deficiency 10.7
45 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 10.7
46 coenzyme q10 deficiency, primary, 3 10.7
47 mitochondrial infantile bilateral striatal necrosis 10.7
48 mitochondrial complex ii deficiency 10.7
49 dermatophytosis 10.6 BCS1L MT-ND1 MT-ND4 MT-ND5 MT-ND6 NDUFS4
50 multiminicore disease 10.6 BCS1L MT-ATP6 MT-ND1 MT-ND3 MT-ND4 MT-ND5

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:

54

Growth- Other:
failure to thrive

Muscle Soft Tissue:
hypotonia

Head And Neck- Eyes:
optic atrophy
nystagmus
strabismus
ptosis
pigmentary retinopathy
more
Laboratory- Abnormalities:
increased csf lactate
increased serum lactate

Respiratory:
respiratory failure
abnormal respiratory patterns

Neurologic- Central Nervous System:
hypotonia
mental retardation
dystonia
dysarthria
ataxia
more
Skin Nails & Hair- Hair:
hypertrichosis

Neurologic- Behavioral Psychiatric Manifestations:
emotional lability

Metabolic Features:
lactic acidosis


Clinical features from OMIM:

256000

Human phenotypes related to Leigh Syndrome:

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

UMLS symptoms related to Leigh Syndrome:


ataxia, muscle spasticity, ophthalmoplegia, seizures

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

26
id 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 NDUFA9 NDUFS7 NDUFA10
6 Increased shRNA abundance (Z-score > 2) GR00366-A-120 9.8 NDUFS7 NDUFA10
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 NDUFA9 NDUFA10
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 NDUFA9 NDUFS7 NDUFA10 NDUFA2
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 9.35 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)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cysteamine Approved, Investigational Phase 2 60-23-1 6058
2 Tocopherol Approved, 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)

id 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 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
4 The KHENERGY Study Recruiting NCT02909400 Phase 2 KH176;placebo
5 EPI-743 for Mitochondrial Respiratory Chain Diseases Active, not recruiting NCT01370447 Phase 2 EPI-743
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:

id Genetic test Affiliating Genes
1 Leigh Syndrome (nuclear Dna Mutation) 29 24 BCS1L COX10 DLD MTFMT NDUFA1 NDUFA10 NDUFAF2 NDUFAF6 NDUFS1 NDUFS3 NDUFS4 NDUFS7 NDUFS8 NDUFV1 SCO1 SCO2 SDHA SURF1 FOXRED1
2 Leigh Syndrome 29
3 Leigh Syndrome Due to Mitochondrial Complex Ii Deficiency 29
4 Leigh Syndrome Due to Mitochondrial Complex I Deficiency 29 24 NDUFA2 NDUFA12 NDUFA9
5 Leigh Syndrome (mtdna Mutation) 29 24
6 Leigh Syndrome Due to Mitochondrial Complex Iii Deficiency 29
7 Leigh Syndrome (mtdna Deletion) 24

Anatomical Context for Leigh Syndrome

MalaCards organs/tissues related to Leigh Syndrome:

39
Cerebellum, Spinal Cord, Thalamus, Kidney, Eye, Brain, Heart

Publications for Leigh Syndrome

Articles related to Leigh Syndrome:

(show top 50) (show all 209)
id Title Authors Year
1
NDUFAF4 variants are associated with Leigh syndrome and cause a specific mitochondrial complex I assembly defect. ( 28853723 )
2017
2
Novel mutation of ND4 gene identified by targeted next-generation sequencing in patient with Leigh syndrome. ( 27761019 )
2017
3
Premature Ovarian Failure in French Canadian Leigh Syndrome. ( 28284481 )
2017
4
Do lesional perfusion abnormalities on arterial spin labeling truly contribute to the diagnosis of Leigh syndrome? ( 27826676 )
2017
5
Direct effects of mitochondrial dysfunction on poor bone health in Leigh syndrome. ( 28899781 )
2017
6
Correction for Ferrari et al., Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome. ( 28584118 )
2017
7
Management of Leigh Syndrome: current status and new insights. ( 28905387 )
2017
8
Involvement of Cerebellum in Leigh Syndrome: Case Report and Review of the Literature. ( 28739363 )
2017
9
Modulation of mitochondrial dysfunction-related oxidative stress in fibroblasts of patients with Leigh syndrome by inhibition of prooxidative p66Shc pathway. ( 28739512 )
2017
10
Bioenergetic Impairment in Congenital Muscular Dystrophy Type 1A and Leigh Syndrome Muscle Cells. ( 28367954 )
2017
11
Response to correspondence of NDUFS4-related Leigh syndrome in Hutterites. ( 28371264 )
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
Japanese Leigh syndrome case treated with EPI-743. ( 28916229 )
2017
14
AAV9-based gene therapy partially ameliorates the clinical phenotype of a mouse model of Leigh syndrome. ( 28753212 )
2017
15
Head Trauma as a Precipitating Factor for Late-onset Leigh Syndrome: a Case Report. ( 28286850 )
2017
16
Defective mitochondrial RNA processing due to PNPT1 variants causes Leigh syndrome. ( 28645153 )
2017
17
NDUFS4-related Leigh syndrome in Hutterites. ( 28371352 )
2017
18
Why does Leigh syndrome respond to immunotherapy? ( 28649511 )
2017
19
Widening the Heterogeneity of Leigh Syndrome: Clinical, Biochemical, and Neuroradiologic Features in a Patient Harboring a NDUFA10 Mutation. ( 28247337 )
2017
20
Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome. ( 28483998 )
2017
21
Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome. ( 28777931 )
2017
22
Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients. ( 28429146 )
2017
23
Schizophrenia-like symptoms in a patient with Leigh syndrome. ( 28262162 )
2017
24
The pleiotropic effects of decanoic acid treatment on mitochondrial function in fibroblasts from patients with complex I deficient Leigh syndrome. ( 27080638 )
2016
25
Generation of a human iPSC line from a patient with Leigh syndrome. ( 27345786 )
2016
26
Novel mutation in mitochondrial DNA in 2 siblings with Leigh syndrome. ( 27574709 )
2016
27
Leigh Syndrome in Childhood: Neurologic Progression and Functional Outcome. ( 27074294 )
2016
28
Affection of the frontal lobe in Leigh syndrome due to the m.8993T>G mutation. ( 27209570 )
2016
29
Response to immunotherapy in a patient with adult onset Leigh syndrome and T9176C mtDNA mutation. ( 27408822 )
2016
30
Respiratory chain inhibition: one more feature to propose MPTP intoxication as a Leigh syndrome model. ( 27787743 )
2016
31
Rostral brain lesions of Leigh syndrome associated with the mitochondrial DNA 8993T>G mutation. ( 27000225 )
2016
32
The neuroimaging of Leigh syndrome: case series and review of the literature. ( 26739140 )
2016
33
Ophthalmologic involvement in Leigh syndrome. ( 27226419 )
2016
34
Mutations in mitochondrial complex I assembly factor NDUFAF3 cause Leigh syndrome. ( 27986404 )
2016
35
Significance of rostral brain lesions of Leigh syndrome associated with the mitochondrial DNA 8993T>G mutation. ( 27206685 )
2016
36
DNM1L-related encephalopathy in infancy with Leigh syndrome-like phenotype and suppression-burst. ( 27301544 )
2016
37
Free-thiamine is a potential biomarker of thiamine transporter-2 deficiency: a treatable cause of Leigh syndrome. ( 26657515 )
2016
38
Leigh syndrome associated with a novel mutation in the COX15 gene. ( 26959537 )
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
FDG-PET study of patients with Leigh syndrome. ( 26944169 )
2016
41
Transient symmetric T2-hyperintensities of basal ganglia and brainstem not only point to Leigh syndrome. ( 27570408 )
2016
42
Ophthalmologic involvement in Leigh syndrome. ( 27234010 )
2016
43
SLC25A46 is required for mitochondrial lipid homeostasis and cristae maintenance and is responsible for Leigh syndrome. ( 27390132 )
2016
44
Identification of a novel deletion in SURF1 gene: Heterogeneity in Leigh syndrome with COX deficiency. ( 27756633 )
2016
45
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
46
Response to letter to the editor: Why does Leigh syndrome responds to immunotherapy? ( 27547733 )
2016
47
Ndufs4 related Leigh syndrome: A case report and review of the literature. ( 27079373 )
2016
48
Leigh syndrome: Resolving the clinical and genetic heterogeneity paves the way for treatment options. ( 26725255 )
2016
49
Ophthalmological characteristics in children with Leigh syndrome - A long-term follow-up. ( 26893257 )
2016
50
Spasticity secondary to Leigh syndrome managed with selective dorsal rhizotomy: a case report. ( 27041374 )
2016

Variations for Leigh Syndrome

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

71 (show all 35)
id 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 74)
id 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 NDUFAF2 NDUFAF2, 1-BP DEL, 103A deletion Pathogenic
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.595C> T (p.Arg199Trp) single nucleotide variant Pathogenic rs104894270 GRCh37 Chromosome 11, 47603988: 47603988
5 BCS1L NM_004328.4(BCS1L): c.296C> T (p.Pro99Leu) single nucleotide variant Pathogenic rs121908572 GRCh37 Chromosome 2, 219526006: 219526006
6 NDUFS4 NM_002495.3(NDUFS4): c.316C> T (p.Arg106Ter) single nucleotide variant Pathogenic rs104893898 GRCh37 Chromosome 5, 52942201: 52942201
7 NDUFS4 NDUFS4, IVS1AS, G-A, -1 single nucleotide variant Pathogenic
8 NDUFA2 NDUFA2, IVS2DS, G-A, +5 single nucleotide variant Pathogenic
9 NDUFS7 NM_024407.4(NDUFS7): c.364G> A (p.Val122Met) single nucleotide variant Pathogenic rs104894705 GRCh37 Chromosome 19, 1391005: 1391005
10 NDUFS7 NM_024407.4(NDUFS7): c.434G> A (p.Arg145His) single nucleotide variant Pathogenic rs121434479 GRCh37 Chromosome 19, 1391143: 1391143
11 NDUFS7 NDUFS7, IVS1AS, C-G, -1167 single nucleotide variant Pathogenic
12 MT-TV m.1624C> T single nucleotide variant Pathogenic rs199476144 GRCh37 Chromosome MT, 1624: 1624
13 MT-TW m.5537_5538insT insertion Pathogenic rs199474672 GRCh37 Chromosome MT, 5537: 5538
14 MT-TK m.8363G> A single nucleotide variant Pathogenic rs118192100 GRCh37 Chromosome MT, 8363: 8363
15 MT-TL1 m.3243A> G single nucleotide variant Pathogenic rs199474657 GRCh37 Chromosome MT, 3243: 3243
16 MT-ATP6 m.8993T> G single nucleotide variant Pathogenic rs199476133 GRCh37 Chromosome MT, 8993: 8993
17 MT-ATP6 m.8993T> C single nucleotide variant Pathogenic rs199476133 GRCh37 Chromosome MT, 8993: 8993
18 MT-ATP6 m.9176T> C single nucleotide variant Pathogenic rs199476135 GRCh37 Chromosome MT, 9176: 9176
19 MT-ATP6 m.8851T> C single nucleotide variant Pathogenic rs199476136 GRCh37 Chromosome MT, 8851: 8851
20 MT-ATP6 m.9185T> C single nucleotide variant Pathogenic rs199476138 GRCh37 Chromosome MT, 9185: 9185
21 MT-ATP6 m.9176T> G single nucleotide variant Pathogenic rs199476135 GRCh37 Chromosome MT, 9176: 9176
22 MT-CO3 m.9537dupC duplication Pathogenic rs267606614 GRCh37 Chromosome MT, 9537: 9537
23 MT-ND6 NC_012920.1: m.14484T> C single nucleotide variant Pathogenic/Likely pathogenic rs199476104 GRCh37 Chromosome MT, 14484: 14484
24 MT-ND6 m.14459G> A single nucleotide variant Pathogenic rs199476105 GRCh37 Chromosome MT, 14459: 14459
25 MT-ND6 m.14487T> C single nucleotide variant Pathogenic rs199476109 GRCh37 Chromosome MT, 14487: 14487
26 MT-ND5 m.12706T> C single nucleotide variant Pathogenic rs267606893 GRCh37 Chromosome MT, 12706: 12706
27 MT-ND5 m.13045A> C single nucleotide variant Pathogenic rs267606895 GRCh37 Chromosome MT, 13045: 13045
28 MT-ND5 m.13084A> T single nucleotide variant Pathogenic rs267606896 GRCh37 Chromosome MT, 13084: 13084
29 MT-ND5; MT-TL1 m.13513G> A single nucleotide variant Pathogenic rs267606897 GRCh37 Chromosome MT, 13513: 13513
30 MT-ND5 m.13042G> A single nucleotide variant Pathogenic rs267606898 GRCh37 Chromosome MT, 13042: 13042
31 MT-ND4 m.11777C> A single nucleotide variant Pathogenic rs28384199 GRCh37 Chromosome MT, 11777: 11777
32 MT-ND3 m.10191T> C single nucleotide variant Pathogenic rs267606890 GRCh37 Chromosome MT, 10191: 10191
33 MT-ND3 m.10158T> C single nucleotide variant Pathogenic rs199476117 GRCh37 Chromosome MT, 10158: 10158
34 MT-ND3 m.10197G> A single nucleotide variant Pathogenic rs267606891 GRCh37 Chromosome MT, 10197: 10197
35 MT-ND2 m.4681T> C single nucleotide variant Pathogenic rs267606889 GRCh37 Chromosome MT, 4681: 4681
36 MT-ND1 NC_012920.1: m.3460G> A single nucleotide variant Pathogenic rs199476118 GRCh37 Chromosome MT, 3460: 3460
37 SURF1 NM_003172.3(SURF1): c.845_846delCT (p.Ser282Cysfs) deletion Pathogenic rs782316919 GRCh37 Chromosome 9, 136218825: 136218826
38 NDUFA9 NM_005002.4(NDUFA9): c.962G> C (p.Arg321Pro) single nucleotide variant Pathogenic rs199592341 GRCh37 Chromosome 12, 4794490: 4794490
39 NDUFA10 NM_004544.3(NDUFA10): c.1A> G (p.Met1Val) single nucleotide variant Pathogenic rs387906872 GRCh37 Chromosome 2, 240964718: 240964718
40 NDUFA10 NM_004544.3(NDUFA10): c.425A> G (p.Gln142Arg) single nucleotide variant Pathogenic rs387906873 GRCh37 Chromosome 2, 240960649: 240960649
41 NDUFA12 NM_018838.4(NDUFA12): c.178C> T (p.Arg60Ter) single nucleotide variant Pathogenic rs387907139 GRCh37 Chromosome 12, 95388025: 95388025
42 MTFMT NM_139242.3(MTFMT): c.626C> T (p.Ser209Leu) single nucleotide variant Pathogenic rs201431517 GRCh37 Chromosome 15, 65313871: 65313871
43 MTFMT NM_139242.3(MTFMT): c.994C> T (p.Arg332Ter) single nucleotide variant Pathogenic rs200286768 GRCh37 Chromosome 15, 65295576: 65295576
44 MT-ATP6 m.9191T> C single nucleotide variant Pathogenic rs386829069 GRCh37 Chromosome MT, 9191: 9191
45 NDUFS4 NM_002495.3(NDUFS4): c.462delA (p.Lys154Asnfs) deletion Pathogenic rs587776949 GRCh38 Chromosome 5, 53683155: 53683155
46 MT-ND1 NC_012920.1: m.3481G> A single nucleotide variant Pathogenic rs587776433 GRCh37 Chromosome MT, 3481: 3481
47 MT-ND1 NC_012920.1: m.3890G> A single nucleotide variant Pathogenic rs587776434 GRCh37 Chromosome MT, 3890: 3890
48 MT-TW NC_012920.1: m.5523T> G single nucleotide variant Pathogenic rs587776435 GRCh37 Chromosome MT, 5523: 5523
49 MT-TW NC_012920.1: m.5559A> G single nucleotide variant Pathogenic rs370471013 GRCh37 Chromosome MT, 5559: 5559
50 MT-CO3 NC_012920.1: m.9478T> C single nucleotide variant Pathogenic rs587776437 GRCh37 Chromosome MT, 9478: 9478

Expression for Leigh Syndrome

Search GEO for disease gene expression data for Leigh Syndrome.

Pathways for Leigh Syndrome

GO Terms for Leigh Syndrome

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

id Name GO ID Score Top Affiliating Genes
1 mitochondrial membrane GO:0031966 9.92 COX15 MT-ND1 MT-ND3 MT-ND4 MT-ND6 NDUFA2
2 mitochondrial matrix GO:0005759 9.8 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 9.63 NDUFA10 NDUFS3 SDHA
5 mitochondrial respiratory chain GO:0005746 9.43 COX15 SURF1
6 mitochondrial respiratory chain complex I GO:0005747 9.4 MT-ND1 MT-ND3 MT-ND4 MT-ND5 NDUFA10 NDUFA12
7 membrane GO:0016020 10.3 BCS1L COX15 MT-ATP6 MT-ND1 MT-ND3 MT-ND4
8 mitochondrial inner membrane GO:0005743 10.21 BCS1L COX15 MT-ATP6 MT-ND1 MT-ND3 MT-ND4
9 mitochondrion GO:0005739 10.09 BCS1L COX15 MT-ND1 MT-ND3 MT-ND4 MT-ND5

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

(show all 12)
id Name GO ID Score Top Affiliating Genes
1 mitochondrial respiratory chain complex I assembly GO:0032981 9.86 BCS1L MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6
2 response to oxidative stress GO:0006979 9.67 MT-ND3 NDUFA12 NDUFS8
3 cellular respiration GO:0045333 9.65 COX15 MT-ND1 NDUFAF2 NDUFS3 NDUFS4
4 ATP biosynthetic process GO:0006754 9.51 MT-ATP6 SURF1
5 reactive oxygen species metabolic process GO:0072593 9.5 NDUFAF2 NDUFS3 NDUFS4
6 respiratory electron transport chain GO:0022904 9.48 NDUFAF2 SDHA
7 mitochondrial respiratory chain complex IV assembly GO:0033617 9.46 BCS1L SURF1
8 mitochondrial electron transport, NADH to ubiquinone GO:0006120 9.44 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFA10
9 respiratory chain complex IV assembly GO:0008535 9.43 COX15 SURF1
10 electron transport chain GO:0022900 9.4 NDUFS4 SDHA
11 ATP synthesis coupled electron transport GO:0042773 9.37 MT-ND4 MT-ND5
12 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:

id 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 electron carrier activity GO:0009055 9.62 NDUFA12 NDUFAF2 NDUFS3 SDHA
3 NADH dehydrogenase (ubiquinone) activity GO:0008137 9.47 MT-ND1 MT-ND3 MT-ND4 MT-ND5 MT-ND6 NDUFA10
4 oxidoreductase activity, acting on NAD(P)H GO:0016651 9.43 NDUFS3 NDUFS4 NDUFS8
5 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.4 COX15 SDHA
6 cytochrome-c oxidase activity GO:0004129 9.37 COX15 SURF1
7 NADH dehydrogenase activity GO:0003954 9.26 NDUFA9 NDUFS3 NDUFS7 NDUFS8

Sources for Leigh Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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