CSS2
MCID: CFF007
MIFTS: 41

Coffin-Siris Syndrome 2 (CSS2)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases, Smell/Taste diseases

Aliases & Classifications for Coffin-Siris Syndrome 2

MalaCards integrated aliases for Coffin-Siris Syndrome 2:

Name: Coffin-Siris Syndrome 2 56 12 73 15
Mental Retardation, Autosomal Dominant 14 56 73 29 13 6 71
Mrd14 56 12 73
Css2 56 12 73
Mental Retardation, Autosomal Dominant 14; Mrd14 56
Autosomal Dominant Mental Retardation 14 12
Coffin-Siris Syndrome, Type 2 39

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant


HPO:

31
coffin-siris syndrome 2:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Coffin-Siris Syndrome 2

OMIM : 56 Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Other more variable features may also occur. Patients with ARID1A mutations have a wide spectrum of manifestations, from severe intellectual disability and serious internal complications that could result in early death to mild intellectual disability (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900). The chromosome 1p36.11 duplication syndrome, in which the ARID1A gene is duplicated, is characterized by impaired intellectual development, microcephaly, dysmorphic facial features, and hand and foot anomalies. (614607)

MalaCards based summary : Coffin-Siris Syndrome 2, also known as mental retardation, autosomal dominant 14, is related to ovarian carcinosarcoma and breast pericanalicular fibroadenoma. An important gene associated with Coffin-Siris Syndrome 2 is ARID1A (AT-Rich Interaction Domain 1A), and among its related pathways/superpathways are Glycosaminoglycan metabolism and Chondroitin sulfate/dermatan sulfate metabolism. Affiliated tissues include heart, bone and brain, and related phenotypes are short stature and seizure

Disease Ontology : 12 A Coffin-Siris syndrome that has material basis in an autosomal dominant mutation of ARID1A on chromosome 1p36.11.

UniProtKB/Swiss-Prot : 73 Coffin-Siris syndrome 2: A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported.

Related Diseases for Coffin-Siris Syndrome 2

Graphical network of the top 20 diseases related to Coffin-Siris Syndrome 2:



Diseases related to Coffin-Siris Syndrome 2

Symptoms & Phenotypes for Coffin-Siris Syndrome 2

Human phenotypes related to Coffin-Siris Syndrome 2:

31 (show all 31)
# Description HPO Frequency HPO Source Accession
1 short stature 31 occasional (7.5%) HP:0004322
2 seizure 31 occasional (7.5%) HP:0001250
3 coarse facial features 31 very rare (1%) HP:0000280
4 feeding difficulties 31 very rare (1%) HP:0011968
5 thick lower lip vermilion 31 very rare (1%) HP:0000179
6 wide mouth 31 very rare (1%) HP:0000154
7 sparse scalp hair 31 very rare (1%) HP:0002209
8 long eyelashes 31 very rare (1%) HP:0000527
9 recurrent infections 31 very rare (1%) HP:0002719
10 abnormal corpus callosum morphology 31 very rare (1%) HP:0001273
11 absent fifth fingernail 31 very rare (1%) HP:0200104
12 absent fifth toenail 31 very rare (1%) HP:0200105
13 macroglossia 31 HP:0000158
14 intellectual disability 31 HP:0001249
15 global developmental delay 31 HP:0001263
16 delayed skeletal maturation 31 HP:0002750
17 depressed nasal bridge 31 HP:0005280
18 delayed speech and language development 31 HP:0000750
19 anteverted nares 31 HP:0000463
20 visual impairment 31 HP:0000505
21 thick eyebrow 31 HP:0000574
22 brachydactyly 31 HP:0001156
23 low anterior hairline 31 HP:0000294
24 wide nose 31 HP:0000445
25 abnormality of cardiovascular system morphology 31 HP:0030680
26 abnormal heart morphology 31 HP:0001627
27 generalized hypotonia 31 HP:0001290
28 small nail 31 HP:0001792
29 abnormality of the pinna 31 HP:0000377
30 hypertrichosis 31 HP:0000998
31 aplasia/hypoplasia of the distal phalanges of the hand 31 HP:0009835

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Mouth:
macroglossia
large mouth
thin upper vermilion
thick lower vermilion

Skeletal Hands:
brachydactyly
hypoplastic to absent terminal phalanges (especially fifth finger)

Neurologic Central Nervous System:
hypotonia
mental retardation
seizures (in some patients)
speech delay
delayed psychomotor development
more
Skin Nails Hair Nails:
hypoplastic nails

Head And Neck Face:
coarse facies

Abdomen Gastrointestinal:
feeding problems

Growth Height:
short stature (in some patients)

Skeletal Feet:
hypoplastic to absent terminal phalanges (especially fifth toe)

Head And Neck Eyes:
visual impairment
long eyelashes
thick eyebrows

Skin Nails Hair Hair:
sparse scalp hair
hypertrichosis
low frontal hairline

Head And Neck Nose:
anteverted nostrils
broad nose
flat nasal bridge

Skeletal:
delayed bone age

Cardiovascular Heart:
congenital heart defects

Head And Neck Ears:
malformed ears

Head And Neck Teeth:
delayed dentition

Clinical features from OMIM:

614607

Drugs & Therapeutics for Coffin-Siris Syndrome 2

Search Clinical Trials , NIH Clinical Center for Coffin-Siris Syndrome 2

Genetic Tests for Coffin-Siris Syndrome 2

Genetic tests related to Coffin-Siris Syndrome 2:

# Genetic test Affiliating Genes
1 Mental Retardation, Autosomal Dominant 14 29 ARID1A

Anatomical Context for Coffin-Siris Syndrome 2

MalaCards organs/tissues related to Coffin-Siris Syndrome 2:

40
Heart, Bone, Brain

Publications for Coffin-Siris Syndrome 2

Articles related to Coffin-Siris Syndrome 2:

(show all 23)
# Title Authors PMID Year
1
A comprehensive molecular study on Coffin-Siris and Nicolaides-Baraitser syndromes identifies a broad molecular and clinical spectrum converging on altered chromatin remodeling. 6 56
23906836 2013
2
Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients. 6 56
23929686 2013
3
Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. 6 56
22426308 2012
4
Microduplication of the ARID1A gene causes intellectual disability with recognizable syndromic features. 56
27906199 2017
5
Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A. 56
25168959 2014
6
190-kb duplication in 1p36.11 including PIGV and ARID1A genes in a girl with intellectual disability and hexadactyly. 56
23521658 2013
7
The three-dimensional structure of the toxic peptide Cl13 from the scorpion Centruroides limpidus. 61
32569846 2020
8
Persistence of Nasopharyngeal Pneumococcal Vaccine Serotypes and Increase of Nonvaccine Serotypes Among Vaccinated Infants and Their Mothers 5 Years After Introduction of Pneumococcal Conjugate Vaccine 13 in The Gambia. 61
30165376 2019
9
Design and expression of recombinant toxins from Mexican scorpions of the genus Centruroides for production of antivenoms. 61
28126552 2017
10
Mapping of a FEB3 homologous febrile seizure locus on mouse chromosome 2 containing candidate genes Scn1a and Scn3a. 61
27690330 2016
11
Effect on nasopharyngeal pneumococcal carriage of replacing PCV7 with PCV13 in the Expanded Programme of Immunization in The Gambia. 61
26592141 2015
12
Is Speed Reserve Related to Critical Speed and Anaerobic Distance Capacity in Swimming? 61
24513615 2015
13
Study of expression of TLR2, TLR4 and transckription factor NF-kB structures of galt of rats in the conditions of the chronic social stress and modulation of structure of intestinal microflora. 61
24423688 2013
14
Chondroitin sulfate synthase-2 is necessary for chain extension of chondroitin sulfate but not critical for skeletal development. 61
22952769 2012
15
Structural basis of neutralization of the major toxic component from the scorpion Centruroides noxius Hoffmann by a human-derived single-chain antibody fragment. 61
21489992 2011
16
Exploiting cross-reactivity to neutralize two different scorpion venoms with one single chain antibody fragment. 61
21156801 2011
17
Chondroitin sulfate synthase-2/chondroitin polymerizing factor has two variants with distinct function. 61
20729547 2010
18
Phenotyping mouse chromosome substitution strains reveal multiple QTLs for febrile seizure susceptibility. 61
19077119 2009
19
Expression of calpain small subunit 2 in mammalian tissues. 61
15590481 2004
20
Differential distribution of calpain small subunit 1 and 2 in rat brain. 61
15078555 2004
21
A novel human small subunit of calpains. 61
11853546 2002
22
Influence of pharmacokinetic model on vancomycin peak concentration targets. 61
8721276 1996
23
Coherent beam and image amplification by Brillouin two-beam coupling in CSS2. 61
19768025 1990

Variations for Coffin-Siris Syndrome 2

ClinVar genetic disease variations for Coffin-Siris Syndrome 2:

6 (show all 24) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ARID1A NM_006015.6(ARID1A):c.921_940del (p.Tyr308fs)deletion Pathogenic 434335 rs1553146165 1:27023808-27023827 1:26697317-26697336
2 ARID1A NM_006015.6(ARID1A):c.5164C>T (p.Arg1722Ter)SNV Pathogenic 434343 rs1485978447 1:27105553-27105553 1:26779062-26779062
3 ARID1A NM_006015.6(ARID1A):c.1348C>T (p.Gln450Ter)SNV Pathogenic 560946 rs1557591264 1:27056352-27056352 1:26729861-26729861
4 ARID1A NM_006015.6(ARID1A):c.6134_6138del (p.Lys2045fs)deletion Pathogenic 560947 rs1557620758 1:27106523-27106527 1:26780032-26780036
5 ARID1A NM_006015.6(ARID1A):c.750_771dup (p.Ser258fs)duplication Pathogenic 623658 rs1557570794 1:27023643-27023644 1:26697152-26697153
6 ARID1A NM_006015.6(ARID1A):c.2879-1G>ASNV Pathogenic 812670 1:27092947-27092947 1:26766456-26766456
7 ARID1A NM_006015.6(ARID1A):c.5693del (p.Pro1898fs)deletion Pathogenic 816871 1:27106078-27106078 1:26779587-26779587
8 ARID1A NM_006015.6(ARID1A):c.31_56del (p.Ser11fs)deletion Pathogenic 30292 rs797045262 1:27022913-27022938 1:26696422-26696447
9 ARID1A NM_006015.6(ARID1A):c.2758C>T (p.Gln920Ter)SNV Pathogenic 30293 rs387906845 1:27092737-27092737 1:26766246-26766246
10 ARID1A NM_006015.6(ARID1A):c.4003C>T (p.Arg1335Ter)SNV Pathogenic 30294 rs387906846 1:27100207-27100207 1:26773716-26773716
11 ARID1A NM_006015.6(ARID1A):c.394del (p.Val132fs)deletion Pathogenic 210259 rs797045263 1:27023285-27023285 1:26696794-26696794
12 ARID1A NM_006015.6(ARID1A):c.5965C>T (p.Arg1989Ter)SNV Pathogenic 225842 rs879255270 1:27106354-27106354 1:26779863-26779863
13 ARID1A NM_006015.6(ARID1A):c.1113del (p.Gln372fs)deletion Pathogenic 225843 rs875989848 1:27024002-27024002 1:26697511-26697511
14 ARID1A NM_006015.6(ARID1A):c.3679G>T (p.Glu1227Ter)SNV Pathogenic 225844 rs875989849 1:27099442-27099442 1:26772951-26772951
15 ARID1A NM_006015.6(ARID1A):c.5138T>C (p.Leu1713Pro)SNV Likely pathogenic 210260 rs797045264 1:27105527-27105527 1:26779036-26779036
16 ARID1A NM_006015.6(ARID1A):c.3067T>C (p.Trp1023Arg)SNV Likely pathogenic 635055 rs1557612048 1:27094359-27094359 1:26767868-26767868
17 ARID1A NM_006015.6(ARID1A):c.3148G>T (p.Asp1050Tyr)SNV Likely pathogenic 689740 1:27094440-27094440 1:26767949-26767949
18 ARID1A NM_006015.6(ARID1A):c.4860dup (p.Pro1621fs)duplication Likely pathogenic 559859 rs1553153291 1:27101577-27101578 1:26775086-26775087
19 ARID1A NM_006015.6(ARID1A):c.6196A>T (p.Asn2066Tyr)SNV Likely pathogenic 801462 1:27106585-27106585 1:26780094-26780094
20 ARID1A NM_006015.6(ARID1A):c.3408G>A (p.Ala1136=)SNV Conflicting interpretations of pathogenicity 434322 rs146598030 1:27098992-27098992 1:26772501-26772501
21 ARID1A NM_006015.6(ARID1A):c.592C>T (p.Pro198Ser)SNV Uncertain significance 801460 1:27023486-27023486 1:26696995-26696995
22 ARID1A NM_006015.6(ARID1A):c.5015T>G (p.Val1672Gly)SNV Likely benign 801461 1:27102089-27102089 1:26775598-26775598
23 ARID1A NM_006015.6(ARID1A):c.3702C>T (p.Gly1234=)SNV Likely benign 518315 rs376672377 1:27099465-27099465 1:26772974-26772974
24 ARID1A NM_006015.6(ARID1A):c.3978_3980GCA[9] (p.Gln1334dup)short repeat Benign/Likely benign 235338 rs374564889 1:27100181-27100182 1:26773690-26773691

Expression for Coffin-Siris Syndrome 2

Search GEO for disease gene expression data for Coffin-Siris Syndrome 2.

Pathways for Coffin-Siris Syndrome 2

Pathways related to Coffin-Siris Syndrome 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.01 CSGALNACT2 CSGALNACT1 CHPF2 CHPF
2
Show member pathways
11.43 CSGALNACT2 CSGALNACT1 CHPF2 CHPF

GO Terms for Coffin-Siris Syndrome 2

Cellular components related to Coffin-Siris Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 SWI/SNF complex GO:0016514 9.26 SMARCE1 ARID1A
2 nBAF complex GO:0071565 9.16 SMARCE1 ARID1A
3 npBAF complex GO:0071564 8.96 SMARCE1 ARID1A
4 Golgi cisterna membrane GO:0032580 8.92 CSGALNACT2 CSGALNACT1 CHPF2 CHPF

Biological processes related to Coffin-Siris Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin organization GO:0006325 9.67 SMARCE1 H2AC18 ARID2 ARID1A
2 ATP-dependent chromatin remodeling GO:0043044 9.43 SMARCE1 ARID1A
3 proteoglycan biosynthetic process GO:0030166 9.4 CSGALNACT2 CSGALNACT1
4 chondroitin sulfate proteoglycan biosynthetic process GO:0050650 9.32 CSGALNACT2 CSGALNACT1
5 dermatan sulfate proteoglycan biosynthetic process GO:0050651 9.26 CSGALNACT2 CSGALNACT1
6 chondroitin sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process GO:0050653 9.16 CSGALNACT2 CSGALNACT1
7 nucleosome disassembly GO:0006337 9.13 SMARCE1 ARID2 ARID1A
8 chondroitin sulfate biosynthetic process GO:0030206 8.92 CSGALNACT2 CSGALNACT1 CHPF2 CHPF

Molecular functions related to Coffin-Siris Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear receptor binding GO:0016922 9.32 SMARCE1 ARID1A
2 N-acetylgalactosaminyl-proteoglycan 3-beta-glucuronosyltransferase activity GO:0050510 9.26 CHPF2 CHPF
3 glucuronosyl-N-acetylgalactosaminyl-proteoglycan 4-beta-N-acetylgalactosaminyltransferase activity GO:0047238 9.16 CSGALNACT1 CHPF
4 glucuronylgalactosylproteoglycan 4-beta-N-acetylgalactosaminyltransferase activity GO:0047237 8.96 CSGALNACT2 CSGALNACT1
5 acetylgalactosaminyltransferase activity GO:0008376 8.92 CSGALNACT2 CSGALNACT1 CHPF2 CHPF

Sources for Coffin-Siris Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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30 HMDB
31 HPO
32 ICD10
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50 NDF-RT
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56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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