MCID: CCK008
MIFTS: 48

Cockayne Syndrome a

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Ear diseases, Skin diseases, Fetal diseases

Aliases & Classifications for Cockayne Syndrome a

MalaCards integrated aliases for Cockayne Syndrome a:

Name: Cockayne Syndrome a 57 75
Cockayne Syndrome, Type a 57 13 40
Csa 57 75
Ckn1 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
phenotypic overlap with xeroderma pigmentosum (see, e.g., )
genetic heterogeneity (see, e.g., cockayne syndrome type b, )


HPO:

32
cockayne syndrome a:
Inheritance heterogeneous autosomal recessive inheritance


Classifications:



Summaries for Cockayne Syndrome a

OMIM : 57 Cockayne syndrome is characterized by abnormal and slow growth and development that becomes evident within the first few years after birth. 'Cachectic dwarfism' describes the outward appearance of afflicted individuals. Other features include cutaneous photosensitivity, thin, dry hair, a progeroid appearance, progressive pigmentary retinopathy, sensorineural hearing loss, dental caries, and a characteristic stance in the ambulatory patient. Patients often show disproportionately long limbs with large hands and feet, and flexion contractures of joints are usual skeletal features. Knee contractures result in a 'horse-riding stance.' There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. The mean age at death in reported cases is 12.5 years, although a few affected individuals have lived into their late teens or twenties. Remarkably, in striking contrast with xeroderma pigmentosum, patients with CS have no significant increase in skin cancer or infection (Nance and Berry, 1992). Lowry (1982) noted that there is an early-onset form of Cockayne syndrome in which patients may show abnormalities at birth and have a shorter survival. Lowry (1982) thus suggested that CS could be divided clinically into the more common type I, with classic CS symptoms that manifest within the first few years or life, and the less common type II, with more severe symptoms that manifest prenatally. Mallery et al. (1998) found no correlation between genotype and phenotype among 16 patients with CS of varying severities, and concluded that clinical differences were based on other genetic backgrounds or the intrauterine environment. (216400)

MalaCards based summary : Cockayne Syndrome a, also known as cockayne syndrome, type a, is related to cockayne syndrome type i and xeroderma pigmentosum, complementation group f. An important gene associated with Cockayne Syndrome a is ERCC8 (ERCC Excision Repair 8, CSA Ubiquitin Ligase Complex Subunit), and among its related pathways/superpathways are DNA Double-Strand Break Repair and Transcription-Coupled Nucleotide Excision Repair (TC-NER). Affiliated tissues include skin, bone and b cells, and related phenotypes are nystagmus and hypertension

UniProtKB/Swiss-Prot : 75 Cockayne syndrome A: A rare disorder characterized by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness. There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. Two clinical forms are recognized: in the classical form or Cockayne syndrome type 1, the symptoms are progressive and typically become apparent within the first few years or life; the less common Cockayne syndrome type 2 is characterized by more severe symptoms that manifest prenatally. Cockayne syndrome shows some overlap with certain forms of xeroderma pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne syndrome do not manifest increased freckling and other pigmentation abnormalities in the skin and have no significant increase in skin cancer.

Related Diseases for Cockayne Syndrome a

Graphical network of the top 20 diseases related to Cockayne Syndrome a:



Diseases related to Cockayne Syndrome a

Symptoms & Phenotypes for Cockayne Syndrome a

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
nystagmus
corneal opacity
optic atrophy
strabismus
decreased lacrimation
more
Neurologic Central Nervous System:
seizures
dementia
cerebral atrophy
mental retardation
normal pressure hydrocephalus
more
Skeletal Spine:
kyphosis
vertebral body abnormalities

Abdomen Liver:
hepatomegaly

Genitourinary Kidneys:
proteinuria
renal failure

Skin Nails Hair Skin:
dry skin
anhidrosis
scarring
photosensitivity
pigmentation
more
Endocrine Features:
hypogonadism
irregular menstrual cycles

Head And Neck Teeth:
malocclusion
delayed eruption of deciduous teeth
dental caries
absent/hypoplastic teeth

Head And Neck Nose:
slender nose

Skeletal Skull:
thickened calvarium

Skeletal Limbs:
mild to moderate joint limitation

Skin Nails Hair:
precociously senile appearance

Skin Nails Hair Hair:
thin, dry hair

Cardiovascular Vascular:
hypertension

Neurologic Peripheral Nervous System:
ataxia
gait disturbance
tremor
peripheral neuropathy
weakness
more
AbdomenSpleen:
splenomegaly

Head And Neck Head:
microcephaly
mandible prognathism

Genitourinary External Genitalia Male:
cryptorchidism
micropenis

Growth Other:
intrauterine growth retardation
cachectic dwarfism
severe postnatal growth deficiency

Head And Neck Face:
loss of facial adipose tissue
wizened face

Head And Neck Ears:
sensorineural hearing loss
malformed ears

Cardiovascular Heart:
cardiac arrhythmias

Skeletal Pelvis:
small, squared off pelvis
hypoplastic iliac wings

Skeletal Hands:
sclerotic ivory phalangeal epiphyses

Muscle Soft Tissue:
decreased subcutaneous adipose tissue

Laboratory Abnormalities:
abnormal myelination in sural nerve biopsies
disturbed visual and brainstem auditory evoked responses indicative of cns demyelination
increased cellular sensitivity to uv light
thymic hormone decreased
at least 2 complementation groups


Clinical features from OMIM:

216400

Human phenotypes related to Cockayne Syndrome a:

32 (show top 50) (show all 66)
# Description HPO Frequency HPO Source Accession
1 nystagmus 32 HP:0000639
2 hypertension 32 HP:0000822
3 intellectual disability 32 HP:0001249
4 seizures 32 HP:0001250
5 ataxia 32 HP:0001251
6 dysarthria 32 HP:0001260
7 gait disturbance 32 HP:0001288
8 muscle weakness 32 HP:0001324
9 tremor 32 HP:0001337
10 kyphosis 32 HP:0002808
11 mandibular prognathia 32 HP:0000303
12 cataract 32 HP:0000518
13 dental malocclusion 32 HP:0000689
14 splenomegaly 32 HP:0001744
15 hepatomegaly 32 HP:0002240
16 carious teeth 32 HP:0000670
17 thickened calvaria 32 HP:0002684
18 microcephaly 32 HP:0000252
19 sensorineural hearing impairment 32 HP:0000407
20 optic atrophy 32 HP:0000648
21 abnormality of visual evoked potentials 32 HP:0000649
22 renal insufficiency 32 HP:0000083
23 proteinuria 32 HP:0000093
24 arrhythmia 32 HP:0011675
25 opacification of the corneal stroma 32 HP:0007759
26 strabismus 32 HP:0000486
27 limitation of joint mobility 32 HP:0001376
28 decreased nerve conduction velocity 32 HP:0000762
29 cryptorchidism 32 HP:0000028
30 dry skin 32 HP:0000958
31 intrauterine growth retardation 32 HP:0001511
32 atypical scarring of skin 32 HP:0000987
33 abnormality of the pinna 32 HP:0000377
34 hypogonadism 32 HP:0000135
35 decreased lacrimation 32 HP:0000633
36 hypoplastic iliac wing 32 HP:0002866
37 dementia 32 HP:0000726
38 hypoplastic pelvis 32 HP:0008839
39 cutaneous photosensitivity 32 HP:0000992
40 abnormality of skin pigmentation 32 HP:0001000
41 sparse hair 32 HP:0008070
42 severe postnatal growth retardation 32 HP:0008850
43 anhidrosis 32 HP:0000970
44 micropenis 32 HP:0000054
45 delayed eruption of primary teeth 32 HP:0000680
46 polyneuropathy 32 HP:0001271
47 cerebral atrophy 32 HP:0002059
48 pigmentary retinopathy 32 HP:0000580
49 menstrual irregularities 32 HP:0000858
50 progeroid facial appearance 32 HP:0005328

GenomeRNAi Phenotypes related to Cockayne Syndrome a according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.53 ERCC6 ERCC8 ERCC4 ERCC5
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.53 ERCC5 ERCC6 ERCC8 ERCC4
3 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-3 9.35 ERCC2 ERCC4 ERCC5 ERCC6 ERCC8

MGI Mouse Phenotypes related to Cockayne Syndrome a:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.55 ERCC2 ERCC4 ERCC5 ERCC6 ERCC8
2 integument MP:0010771 9.26 ERCC2 ERCC5 ERCC6 ERCC8
3 mortality/aging MP:0010768 9.02 ERCC2 ERCC4 ERCC5 ERCC6 ERCC8

Drugs & Therapeutics for Cockayne Syndrome a

Search Clinical Trials , NIH Clinical Center for Cockayne Syndrome a

Genetic Tests for Cockayne Syndrome a

Anatomical Context for Cockayne Syndrome a

MalaCards organs/tissues related to Cockayne Syndrome a:

41
Skin, Bone, B Cells

Publications for Cockayne Syndrome a

Articles related to Cockayne Syndrome a:

(show all 27)
# Title Authors Year
1
Identification of one Novel complex delins mutation and one recurrent mutation of ERCC8 gene in a Chinese family with Cockayne Syndrome A. ( 28273366 )
2017
2
Overexpression of parkin rescues the defective mitochondrial phenotype and the increased apoptosis of Cockayne Syndrome A cells. ( 29262528 )
2017
3
Molecular spectrum of excision repair cross-complementation group 8 gene defects in Chinese patients with Cockayne syndrome type A. ( 29057985 )
2017
4
Overexpression of parkin rescues the defective mitochondrial phenotype and the increased apoptosis of Cockayne Syndrome A cells. ( 27303919 )
2016
5
Cockayne Syndrome: A Diffusion Tensor Imaging and Volumetric Study. ( 27643390 )
2016
6
Metronidazole Toxicity in Cockayne Syndrome: A Case Series. ( 26304821 )
2015
7
Arabidopsis cockayne syndrome A-like proteins 1A and 1B form a complex with CULLIN4 and damage DNA binding protein 1A and regulate the response to UV irradiation. ( 20622147 )
2010
8
Prenatal diagnosis of Cockayne syndrome type A based on the identification of two novel mutations in the ERCC8 gene. ( 19309286 )
2009
9
Association between common genetic variation in Cockayne syndrome A and B genes and nucleotide excision repair capacity among smokers. ( 18708399 )
2008
10
Complementation of the oxidatively damaged DNA repair defect in Cockayne syndrome A and B cells by Escherichia coli formamidopyrimidine DNA glycosylase. ( 17512460 )
2007
11
Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype-phenotype relationship. ( 17276014 )
2007
12
Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo. ( 16916636 )
2006
13
Cockayne syndrome type A: novel mutations in eight typical patients. ( 16865293 )
2006
14
Characterisation of novel mutations in Cockayne syndrome type A and xeroderma pigmentosum group C subjects. ( 15744458 )
2005
15
CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common polymorphism. ( 14661080 )
2004
16
Myocardial ischemia and delayed recovery after anesthesia in a patient with Cockayne syndrome: a case report. ( 11732042 )
2001
17
Molecular cloning and characterization of Saccharomyces cerevisiae RAD28, the yeast homolog of the human Cockayne syndrome A (CSA) gene. ( 8830695 )
1996
18
Cockayne syndrome--a primary defect in DNA repair, transcription, both or neither? ( 8831289 )
1996
19
Cockayne syndrome: a case with hyperinsulinemia and growth hormone deficiency. ( 8068222 )
1994
20
Cockayne syndrome: a case report. ( 7810287 )
1994
21
Demyelinating peripheral neuropathy in Cockayne syndrome: a histopathologic and morphometric study. ( 1320347 )
1992
22
Cockayne syndrome--a case report, and a review of the premature aging syndromes in paediatrics. ( 1784111 )
1991
23
Rare syndromes. I. Cockayne syndrome: a review of the 129 cases so far reported in the literature. ( 3334173 )
1987
24
Cockayne syndrome (a case report). ( 3612583 )
1987
25
Host cell reactivation of ultraviolet light irradiated adenovirus 5 in fibroblasts from patients with Cockayne syndrome: a study with six Japanese cases. ( 6481688 )
1984
26
Eccrine sweat gland anatomy in cockayne syndrome: a possible diagnostic aid. ( 6687286 )
1983
27
Cockayne syndrome: a cellular sensitivity to ultraviolet light. ( 887325 )
1977

Variations for Cockayne Syndrome a

UniProtKB/Swiss-Prot genetic disease variations for Cockayne Syndrome a:

75
# Symbol AA change Variation ID SNP ID
1 ERCC8 p.Ala160Val VAR_025380 rs121434325
2 ERCC8 p.Ala205Pro VAR_025381 rs121434326
3 ERCC8 p.Ala160Thr VAR_063507 rs281875222
4 ERCC8 p.Trp194Cys VAR_063508 rs281875223
5 ERCC8 p.Leu202Ser VAR_063509 rs281875224
6 ERCC8 p.Asp266Gly VAR_063510 rs281875225

ClinVar genetic disease variations for Cockayne Syndrome a:

6
(show all 19)
# Gene Variation Type Significance SNP ID Assembly Location
1 ERCC8 NM_000082.3(ERCC8): c.37G> T (p.Glu13Ter) single nucleotide variant Pathogenic rs121434324 GRCh38 Chromosome 5, 60944972: 60944972
2 ERCC8 ERCC8, 279-BP DEL, 81-BP DEL deletion Pathogenic
3 ERCC8 NM_000082.3(ERCC8): c.966C> A (p.Tyr322Ter) single nucleotide variant Pathogenic rs121434323 GRCh37 Chromosome 5, 60186791: 60186791
4 ERCC8 NM_000082.3(ERCC8): c.966C> A (p.Tyr322Ter) single nucleotide variant Pathogenic rs121434323 GRCh38 Chromosome 5, 60890964: 60890964
5 ERCC8 NM_000082.3(ERCC8): c.37G> T (p.Glu13Ter) single nucleotide variant Pathogenic rs121434324 GRCh37 Chromosome 5, 60240799: 60240799
6 ERCC8 NM_000082.3(ERCC8): c.479C> T (p.Ala160Val) single nucleotide variant Likely pathogenic rs121434325 GRCh37 Chromosome 5, 60200621: 60200621
7 ERCC8 NM_000082.3(ERCC8): c.479C> T (p.Ala160Val) single nucleotide variant Likely pathogenic rs121434325 GRCh38 Chromosome 5, 60904794: 60904794
8 ERCC8 NM_000082.3(ERCC8): c.613G> C (p.Ala205Pro) single nucleotide variant Pathogenic rs121434326 GRCh37 Chromosome 5, 60198273: 60198273
9 ERCC8 NM_000082.3(ERCC8): c.613G> C (p.Ala205Pro) single nucleotide variant Pathogenic rs121434326 GRCh38 Chromosome 5, 60902446: 60902446
10 ERCC8 NM_000082.3(ERCC8): c.141delC (p.Asn47Lysfs) deletion Pathogenic rs786205176 GRCh37 Chromosome 5, 60224723: 60224723
11 ERCC8 NM_000082.3(ERCC8): c.141delC (p.Asn47Lysfs) deletion Pathogenic rs786205176 GRCh38 Chromosome 5, 60928896: 60928896
12 ERCC8 NM_000082.3(ERCC8): c.300C> G (p.Tyr100Ter) single nucleotide variant Pathogenic/Likely pathogenic rs143367518 GRCh37 Chromosome 5, 60214191: 60214191
13 ERCC8 NM_000082.3(ERCC8): c.300C> G (p.Tyr100Ter) single nucleotide variant Pathogenic/Likely pathogenic rs143367518 GRCh38 Chromosome 5, 60918364: 60918364
14 ERCC8 NM_000082.3(ERCC8): c.173+1119G> C single nucleotide variant Pathogenic rs1043679457 GRCh37 Chromosome 5, 60223572: 60223572
15 ERCC8 NM_000082.3(ERCC8): c.173+1119G> C single nucleotide variant Pathogenic rs1043679457 GRCh38 Chromosome 5, 60927745: 60927745
16 ERCC8 NM_000082.3(ERCC8): c.173+1158A> G single nucleotide variant Benign rs4647068 GRCh37 Chromosome 5, 60223533: 60223533
17 ERCC8 NM_000082.3(ERCC8): c.173+1158A> G single nucleotide variant Benign rs4647068 GRCh38 Chromosome 5, 60927706: 60927706
18 ERCC8 NM_000082.3(ERCC8): c.299delAinsAA (p.Tyr100Terfs) indel Pathogenic GRCh37 Chromosome 5, 60214192: 60214192
19 ERCC8 NM_000082.3(ERCC8): c.299delAinsAA (p.Tyr100Terfs) indel Pathogenic GRCh38 Chromosome 5, 60918365: 60918365

Expression for Cockayne Syndrome a

Search GEO for disease gene expression data for Cockayne Syndrome a.

Pathways for Cockayne Syndrome a

Pathways related to Cockayne Syndrome a according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.72 ERCC2 ERCC4 ERCC5 ERCC6 ERCC8
2
Show member pathways
12.29 ERCC2 ERCC4 ERCC5 ERCC6 ERCC8
3
Show member pathways
11.96 ERCC2 ERCC4 ERCC5 ERCC6 ERCC8
4
Show member pathways
11.41 ERCC2 ERCC6
5
Show member pathways
11.09 ERCC2 ERCC4 ERCC5 ERCC6 ERCC8
6 10.9 ERCC2 ERCC4 ERCC6

GO Terms for Cockayne Syndrome a

Cellular components related to Cockayne Syndrome a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleoplasm GO:0005654 9.65 ERCC2 ERCC4 ERCC5 ERCC6 ERCC8
2 transcription factor TFIID complex GO:0005669 9.16 ERCC2 ERCC4
3 holo TFIIH complex GO:0005675 8.96 ERCC2 ERCC5
4 nucleotide-excision repair complex GO:0000109 8.62 ERCC4 ERCC8

Biological processes related to Cockayne Syndrome a according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 9.77 ERCC2 ERCC4 ERCC5 ERCC6 ERCC8
2 response to oxidative stress GO:0006979 9.67 ERCC2 ERCC6 ERCC8
3 nucleotide-excision repair, DNA incision GO:0033683 9.65 ERCC2 ERCC4 ERCC5
4 DNA repair GO:0006281 9.65 ERCC2 ERCC4 ERCC5 ERCC6 ERCC8
5 nucleotide-excision repair, DNA incision, 5-to lesion GO:0006296 9.63 ERCC2 ERCC4 ERCC5
6 nucleotide-excision repair, DNA incision, 3-to lesion GO:0006295 9.61 ERCC2 ERCC4 ERCC5
7 nucleotide-excision repair, preincision complex stabilization GO:0006293 9.58 ERCC2 ERCC4 ERCC5
8 multicellular organism growth GO:0035264 9.56 ERCC2 ERCC6
9 global genome nucleotide-excision repair GO:0070911 9.55 ERCC2 ERCC4
10 transcription elongation from RNA polymerase I promoter GO:0006362 9.54 ERCC2 ERCC6
11 nucleotide-excision repair, preincision complex assembly GO:0006294 9.52 ERCC2 ERCC5
12 response to X-ray GO:0010165 9.51 ERCC6 ERCC8
13 UV protection GO:0009650 9.5 ERCC2 ERCC4 ERCC5
14 nucleotide-excision repair GO:0006289 9.46 ERCC2 ERCC4 ERCC5 ERCC8
15 transcription-coupled nucleotide-excision repair GO:0006283 9.35 ERCC2 ERCC4 ERCC5 ERCC6 ERCC8
16 response to UV GO:0009411 9.02 ERCC2 ERCC4 ERCC5 ERCC6 ERCC8

Molecular functions related to Cockayne Syndrome a according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 9.78 ERCC2 ERCC4 ERCC5 ERCC6
2 hydrolase activity GO:0016787 9.67 ERCC2 ERCC4 ERCC5 ERCC6
3 protein-containing complex binding GO:0044877 9.51 ERCC6 ERCC8
4 helicase activity GO:0004386 9.49 ERCC2 ERCC6
5 nuclease activity GO:0004518 9.46 ERCC4 ERCC5
6 single-stranded DNA binding GO:0003697 9.43 ERCC4 ERCC5
7 endonuclease activity GO:0004519 9.4 ERCC4 ERCC5
8 protein C-terminus binding GO:0008022 9.33 ERCC2 ERCC4 ERCC6
9 endodeoxyribonuclease activity GO:0004520 9.32 ERCC4 ERCC5
10 DNA helicase activity GO:0003678 9.26 ERCC6 ERCC8
11 DNA-dependent ATPase activity GO:0008094 9.13 ERCC2 ERCC6 ERCC8
12 protein N-terminus binding GO:0047485 8.92 ERCC2 ERCC4 ERCC5 ERCC6

Sources for Cockayne Syndrome a

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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