MCID: CRB101
MIFTS: 43

Cerebrooculofacioskeletal Syndrome 1

Categories: Genetic diseases, Bone diseases

Aliases & Classifications for Cerebrooculofacioskeletal Syndrome 1

MalaCards integrated aliases for Cerebrooculofacioskeletal Syndrome 1:

Name: Cerebrooculofacioskeletal Syndrome 1 57 13
Cofs Syndrome 57 76 75 55
Cofs1 57 75
Cerebro-Oculo-Facio-Skeletal Syndrome 1 75
Pena-Shokeir Syndrome, Type Ii 57
Pena-Shokeir Syndrome Type 2 75
Pena Shokeir Syndrome Type 2 73
Cofs Syndrome; Cofs 57
Cofs 57

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
death in childhood


HPO:

32
cerebrooculofacioskeletal syndrome 1:
Mortality/Aging death in infancy death in childhood
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Cerebrooculofacioskeletal Syndrome 1

UniProtKB/Swiss-Prot : 75 Cerebro-oculo-facio-skeletal syndrome 1: A disorder of prenatal onset characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. COFS is considered to be part of the nucleotide-excision repair disorders spectrum that include also xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome.

MalaCards based summary : Cerebrooculofacioskeletal Syndrome 1, also known as cofs syndrome, is related to cerebro-oculo-facio-skeletal syndrome and cerebrooculofacioskeletal syndrome 2. An important gene associated with Cerebrooculofacioskeletal Syndrome 1 is ERCC6 (ERCC Excision Repair 6, Chromatin Remodeling Factor), and among its related pathways/superpathways are DNA Double-Strand Break Repair and Transcription-Coupled Nucleotide Excision Repair (TC-NER). Affiliated tissues include eye and cerebellum, and related phenotypes are thin vermilion border and microcephaly

OMIM : 57 Cerebrooculofacioskeletal syndrome is an autosomal recessive progressive neurodegenerative disorder characterized by microcephaly, congenital cataracts, severe mental retardation, facial dysmorphism, and arthrogryposis (summary by Jaakkola et al., 2010). (214150)

Wikipedia : 76 Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive... more...

Related Diseases for Cerebrooculofacioskeletal Syndrome 1

Graphical network of the top 20 diseases related to Cerebrooculofacioskeletal Syndrome 1:



Diseases related to Cerebrooculofacioskeletal Syndrome 1

Symptoms & Phenotypes for Cerebrooculofacioskeletal Syndrome 1

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
agenesis of corpus callosum
cerebellar hypoplasia
delayed myelination
hypotonia
mental retardation, profound
more
Growth Weight:
failure to thrive
normal or decreased birth weight

Skeletal:
osteoporosis
arthrogryposis

Skeletal Pelvis:
coxa valga
shallow acetabular angle

Skeletal Limbs:
knee flexion contracture
elbow flexion contracture

Skin Nails Hair Hair:
hirsutism

Head And Neck Ears:
sensorineural hearing loss
large ear pinnae

Head And Neck Mouth:
thin lips
upper lip overlaps lower lip

Laboratory Abnormalities:
fibroblasts show hypersensitivity to uv irradiation due to defect in transcription-coupled nucleotide excision repair (tc-ner)

Head And Neck Eyes:
nystagmus
microphthalmia
blepharophimosis
cataracts
deep-set eyes

Head And Neck Head:
microcephaly

Head And Neck Face:
long philtrum
micrognathia
sloping forehead

Skeletal Spine:
kyphoscoliosis

Skeletal Hands:
camptodactyly

Chest Breasts:
widely spaced nipples

Skeletal Feet:
vertical talus
rocker-bottom feet
longitudinal groove on soles
second metatarsal posteriorly placed

Head And Neck Nose:
prominent nasal root


Clinical features from OMIM:

214150

Human phenotypes related to Cerebrooculofacioskeletal Syndrome 1:

32 (show top 50) (show all 60)
# Description HPO Frequency HPO Source Accession
1 thin vermilion border 32 HP:0000233
2 microcephaly 32 hallmark (90%) HP:0000252
3 sloping forehead 32 HP:0000340
4 long philtrum 32 HP:0000343
5 micrognathia 32 hallmark (90%) HP:0000347
6 sensorineural hearing impairment 32 frequent (33%) HP:0000407
7 prominent nasal bridge 32 HP:0000426
8 deeply set eye 32 HP:0000490
9 cataract 32 hallmark (90%) HP:0000518
10 microphthalmia 32 hallmark (90%) HP:0000568
11 blepharophimosis 32 HP:0000581
12 abnormality of the ear 32 HP:0000598
13 nystagmus 32 HP:0000639
14 osteoporosis 32 HP:0000939
15 hirsutism 32 HP:0001007
16 intellectual disability 32 HP:0001249
17 seizures 32 frequent (33%) HP:0001250
18 muscular hypotonia 32 hallmark (90%) HP:0001252
19 agenesis of corpus callosum 32 HP:0001274
20 generalized hypotonia 32 HP:0001290
21 cerebellar hypoplasia 32 HP:0001321
22 failure to thrive 32 HP:0001508
23 rocker bottom foot 32 HP:0001838
24 gliosis 32 HP:0002171
25 intellectual disability, profound 32 HP:0002187
26 coxa valga 32 HP:0002673
27 kyphoscoliosis 32 HP:0002751
28 arthrogryposis multiplex congenita 32 hallmark (90%) HP:0002804
29 elbow flexion contracture 32 HP:0002987
30 deep longitudinal plantar crease 32 HP:0004681
31 knee flexion contracture 32 HP:0006380
32 wide intermamillary distance 32 HP:0006610
33 second metatarsal posteriorly placed 32 HP:0008125
34 joint contracture of the hand 32 HP:0009473
35 camptodactyly 32 HP:0012385
36 delayed myelination 32 HP:0012448
37 hypogonadism 32 frequent (33%) HP:0000135
38 everted lower lip vermilion 32 hallmark (90%) HP:0000232
39 wide nasal bridge 32 hallmark (90%) HP:0000431
40 short neck 32 frequent (33%) HP:0000470
41 visual impairment 32 frequent (33%) HP:0000505
42 optic atrophy 32 occasional (7.5%) HP:0000648
43 cutaneous photosensitivity 32 frequent (33%) HP:0000992
44 hypertonia 32 hallmark (90%) HP:0001276
45 reduced tendon reflexes 32 frequent (33%) HP:0001315
46 joint stiffness 32 hallmark (90%) HP:0001387
47 intrauterine growth retardation 32 frequent (33%) HP:0001511
48 talipes 32 occasional (7.5%) HP:0001883
49 cerebral cortical atrophy 32 hallmark (90%) HP:0002120
50 cerebral calcification 32 hallmark (90%) HP:0002514

GenomeRNAi Phenotypes related to Cerebrooculofacioskeletal Syndrome 1 according to GeneCards Suite gene sharing:

26 (show all 22)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-101 10 ERCC2
2 Increased shRNA abundance (Z-score > 2) GR00366-A-107 10 ERCC6
3 Increased shRNA abundance (Z-score > 2) GR00366-A-115 10 ERCC6
4 Increased shRNA abundance (Z-score > 2) GR00366-A-12 10 ERCC6
5 Increased shRNA abundance (Z-score > 2) GR00366-A-132 10 ERCC6 ERCC2
6 Increased shRNA abundance (Z-score > 2) GR00366-A-136 10 ERCC6
7 Increased shRNA abundance (Z-score > 2) GR00366-A-137 10 ERCC6
8 Increased shRNA abundance (Z-score > 2) GR00366-A-151 10 ERCC6
9 Increased shRNA abundance (Z-score > 2) GR00366-A-159 10 ERCC2
10 Increased shRNA abundance (Z-score > 2) GR00366-A-16 10 ERCC6
11 Increased shRNA abundance (Z-score > 2) GR00366-A-164 10 ERCC6
12 Increased shRNA abundance (Z-score > 2) GR00366-A-166 10 ERCC2
13 Increased shRNA abundance (Z-score > 2) GR00366-A-188 10 ERCC6
14 Increased shRNA abundance (Z-score > 2) GR00366-A-2 10 ERCC6
15 Increased shRNA abundance (Z-score > 2) GR00366-A-201 10 ERCC2
16 Increased shRNA abundance (Z-score > 2) GR00366-A-208 10 ERCC6
17 Increased shRNA abundance (Z-score > 2) GR00366-A-23 10 ERCC6
18 Increased shRNA abundance (Z-score > 2) GR00366-A-25 10 ERCC2
19 Increased shRNA abundance (Z-score > 2) GR00366-A-4 10 ERCC2
20 Increased shRNA abundance (Z-score > 2) GR00366-A-44 10 ERCC6
21 Increased shRNA abundance (Z-score > 2) GR00366-A-80 10 ERCC2
22 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-3 8.8 ERCC2 ERCC5 ERCC6

MGI Mouse Phenotypes related to Cerebrooculofacioskeletal Syndrome 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 integument MP:0010771 8.8 ERCC2 ERCC5 ERCC6

Drugs & Therapeutics for Cerebrooculofacioskeletal Syndrome 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Acute Effects of Coffee Beverage on Postprandial Inflammation and Oxidative Stress - A Pilot Study Active, not recruiting NCT02174640 Not Applicable

Search NIH Clinical Center for Cerebrooculofacioskeletal Syndrome 1

Genetic Tests for Cerebrooculofacioskeletal Syndrome 1

Anatomical Context for Cerebrooculofacioskeletal Syndrome 1

MalaCards organs/tissues related to Cerebrooculofacioskeletal Syndrome 1:

41
Eye, Cerebellum

Publications for Cerebrooculofacioskeletal Syndrome 1

Articles related to Cerebrooculofacioskeletal Syndrome 1:

# Title Authors Year
1
ERCC6 founder mutation identified in Finnish patients with COFS syndrome. ( 20456449 )
2010
2
MICRO syndrome: an entity distinct from COFS syndrome. ( 15216543 )
2004
3
Infantile spasms in COFS syndrome. ( 1930425 )
1991
4
Chondro-osseous changes in Cerebro-Oculo-Facial-Skeletal (COFS) syndrome. ( 7153815 )
1982

Variations for Cerebrooculofacioskeletal Syndrome 1

UniProtKB/Swiss-Prot genetic disease variations for Cerebrooculofacioskeletal Syndrome 1:

75
# Symbol AA change Variation ID SNP ID
1 ERCC6 p.Leu871Pro VAR_063514
2 ERCC6 p.Leu987Pro VAR_063515 rs121917905

ClinVar genetic disease variations for Cerebrooculofacioskeletal Syndrome 1:

6
(show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 ERCC6 ERCC6, 2-BP DEL, 3794AA deletion Pathogenic
2 ERCC6 NM_000124.3(ERCC6): c.2960T> C (p.Leu987Pro) single nucleotide variant Pathogenic rs121917905 GRCh37 Chromosome 10, 50679131: 50679131
3 ERCC6 NM_000124.3(ERCC6): c.2960T> C (p.Leu987Pro) single nucleotide variant Pathogenic rs121917905 GRCh38 Chromosome 10, 49471085: 49471085
4 ERCC6 ERCC6, 2254A-G single nucleotide variant Pathogenic
5 ERCC2 NM_000400.3(ERCC2): c.1846C> T (p.Arg616Trp) single nucleotide variant Pathogenic rs121913024 GRCh37 Chromosome 19, 45856060: 45856060
6 ERCC2 NM_000400.3(ERCC2): c.1846C> T (p.Arg616Trp) single nucleotide variant Pathogenic rs121913024 GRCh38 Chromosome 19, 45352802: 45352802
7 ERCC6 NM_000124.3(ERCC6): c.3862C> T (p.Arg1288Ter) single nucleotide variant Pathogenic rs185142838 GRCh37 Chromosome 10, 50669519: 50669519
8 ERCC6 NM_000124.3(ERCC6): c.3862C> T (p.Arg1288Ter) single nucleotide variant Pathogenic rs185142838 GRCh38 Chromosome 10, 49461473: 49461473
9 ERCC6 NM_000124.3(ERCC6): c.3122A> C (p.Gln1041Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs139007661 GRCh38 Chromosome 10, 49470838: 49470838
10 ERCC6 NM_000124.3(ERCC6): c.3122A> C (p.Gln1041Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs139007661 GRCh37 Chromosome 10, 50678884: 50678884
11 ERCC6 NM_000124.3(ERCC6): c.1996C> T (p.Arg666Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs61760163 GRCh38 Chromosome 10, 49482860: 49482860
12 ERCC6 NM_000124.3(ERCC6): c.1996C> T (p.Arg666Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs61760163 GRCh37 Chromosome 10, 50690906: 50690906
13 ERCC6 NM_000124.3(ERCC6): c.1659G> T (p.Lys553Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs116373975 GRCh37 Chromosome 10, 50708610: 50708610
14 ERCC6 NM_000124.3(ERCC6): c.1659G> T (p.Lys553Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs116373975 GRCh38 Chromosome 10, 49500564: 49500564
15 ERCC6 NM_001346440.1(ERCC6): c.1004delT (p.Leu335Profs) deletion Pathogenic GRCh37 Chromosome 10, 50732472: 50732472
16 ERCC6 NM_001346440.1(ERCC6): c.1004delT (p.Leu335Profs) deletion Pathogenic GRCh38 Chromosome 10, 49524426: 49524426

Expression for Cerebrooculofacioskeletal Syndrome 1

Search GEO for disease gene expression data for Cerebrooculofacioskeletal Syndrome 1.

Pathways for Cerebrooculofacioskeletal Syndrome 1

Pathways related to Cerebrooculofacioskeletal Syndrome 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.55 ERCC2 ERCC5 ERCC6
2
Show member pathways
12.17 ERCC2 ERCC5 ERCC6
3
Show member pathways
11.94 ERCC2 ERCC5 ERCC6
4
Show member pathways
11.37 ERCC2 ERCC6
5
Show member pathways
10.86 ERCC2 ERCC5 ERCC6
6 10.42 ERCC2 ERCC6

GO Terms for Cerebrooculofacioskeletal Syndrome 1

Cellular components related to Cerebrooculofacioskeletal Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 holo TFIIH complex GO:0005675 8.62 ERCC2 ERCC5

Biological processes related to Cerebrooculofacioskeletal Syndrome 1 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 9.65 ERCC2 ERCC5 ERCC6
2 response to oxidative stress GO:0006979 9.54 ERCC2 ERCC6
3 DNA repair GO:0006281 9.54 ERCC2 ERCC5 ERCC6
4 multicellular organism growth GO:0035264 9.52 ERCC2 ERCC6
5 nucleotide-excision repair GO:0006289 9.51 ERCC2 ERCC5
6 nucleotide-excision repair, DNA incision GO:0033683 9.49 ERCC2 ERCC5
7 nucleotide-excision repair, DNA incision, 5-to lesion GO:0006296 9.46 ERCC2 ERCC5
8 transcription elongation from RNA polymerase I promoter GO:0006362 9.43 ERCC2 ERCC6
9 nucleotide-excision repair, preincision complex assembly GO:0006294 9.4 ERCC2 ERCC5
10 nucleotide-excision repair, DNA incision, 3-to lesion GO:0006295 9.32 ERCC2 ERCC5
11 nucleotide-excision repair, preincision complex stabilization GO:0006293 9.26 ERCC2 ERCC5
12 UV protection GO:0009650 9.16 ERCC2 ERCC5
13 transcription-coupled nucleotide-excision repair GO:0006283 9.13 ERCC2 ERCC5 ERCC6
14 response to UV GO:0009411 8.8 ERCC2 ERCC5 ERCC6

Molecular functions related to Cerebrooculofacioskeletal Syndrome 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hydrolase activity GO:0016787 9.5 ERCC2 ERCC5 ERCC6
2 protein C-terminus binding GO:0008022 9.26 ERCC2 ERCC6
3 helicase activity GO:0004386 9.16 ERCC2 ERCC6
4 DNA-dependent ATPase activity GO:0008094 8.96 ERCC2 ERCC6
5 protein N-terminus binding GO:0047485 8.8 ERCC2 ERCC5 ERCC6

Sources for Cerebrooculofacioskeletal Syndrome 1

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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