ARCL2A
MCID: CTS038
MIFTS: 44

Cutis Laxa, Autosomal Recessive, Type Iia (ARCL2A)

Categories: Blood diseases, Bone diseases, Cardiovascular diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Cutis Laxa, Autosomal Recessive, Type Iia

MalaCards integrated aliases for Cutis Laxa, Autosomal Recessive, Type Iia:

Name: Cutis Laxa, Autosomal Recessive, Type Iia 56 13 39 71
Cutis Laxa with Joint Laxity and Retarded Development 56 74 52 73
Arcl2a 56 12 52 73
Cutis Laxa with Growth and Developmental Delay 56 52 73
Cutis Laxa with Bone Dystrophy 56 52 73
Cutis Laxa, Debre Type 56 52 73
Cutis Laxa with Congenital Disorder of Glycosylation 56 73
Autosomal Recessive Cutis Laxa Type Iia 12 15
Arcl2 56 73
Cutis Laxa, Autosomal Recessive Type 2a 52
Cutis Laxa Autosomal Recessive Type Iia 73
Cutis Laxa, Autosomal Recessive, 2a 73
Cl Type Iia 73

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
skin abnormalities tend to decrease with age


HPO:

31
cutis laxa, autosomal recessive, type iia:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Cutis Laxa, Autosomal Recessive, Type Iia

OMIM : 56 Autosomal recessive cutis laxa type II represents a spectrum of clinical entities with variable severity of cutis laxa, abnormal growth, developmental delay, and associated skeletal abnormalities. Aside from cutis laxa, persistent wide fontanels, frontal bossing, slight oxycephaly, downward-slanted palpebral fissures, reversed-V eyebrows, and dental caries are characteristic. Patients with ARCL2 can be divided into 2 major groups: ARCL2A, comprising those with a combined N- and O-linked glycosylation defect (CDG type II), and ARCL2B, those without a metabolic disorder (summary by Morava et al., 2009). Van Maldergem et al. (2008) concluded that ARCL2A should be considered more of a multisystem disorder with cobblestone-like brain dysgenesis manifesting as developmental delay and an epileptic neurodegenerative syndrome rather than purely a dermatologic disorder. For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100). (219200)

MalaCards based summary : Cutis Laxa, Autosomal Recessive, Type Iia, also known as cutis laxa with joint laxity and retarded development, is related to cutis laxa, autosomal dominant 1 and autosomal recessive cutis laxa type ii classic type, and has symptoms including seizures An important gene associated with Cutis Laxa, Autosomal Recessive, Type Iia is ATP6V0A2 (ATPase H+ Transporting V0 Subunit A2), and among its related pathways/superpathways are Degradation of the extracellular matrix and Amino Acid metabolism. Affiliated tissues include skin, eye and bone, and related phenotypes are malar flattening and low-set ears

Disease Ontology : 12 An autosomal recessive cutis laxa type II classic type that has material basis in homozygous or compound heterozygous mutations in the ATP6V0A2 gene on chromosome 12q24.

UniProtKB/Swiss-Prot : 73 Cutis laxa, autosomal recessive, 2A: A disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, a general connective tissue weakness, and varying degrees of growth and developmental delay and neurological abnormalities. Some affected individuals develop seizures and mental deterioration later in life, whereas the skin phenotype tends to become milder with age. At the molecular level, an abnormal glycosylation of serum proteins is observed in many cases.

Wikipedia : 74 De Barsy syndrome is a rare autosomal recessive genetic disorder. Symptoms include cutis laxa (loose... more...

Related Diseases for Cutis Laxa, Autosomal Recessive, Type Iia

Diseases in the Cutis Laxa family:

Cutis Laxa, Autosomal Dominant 1 Cutis Laxa, Autosomal Recessive, Type Ia
Cutis Laxa, Autosomal Recessive, Type Iiia Cutis Laxa, Autosomal Recessive, Type Iia
Cutis Laxa, Autosomal Recessive, Type Iib Cutis Laxa, Autosomal Recessive, Type Ic
Cutis Laxa, Autosomal Dominant 2 Cutis Laxa, Autosomal Recessive, Type Ib
Cutis Laxa, Autosomal Recessive, Type Iiib Cutis Laxa, Autosomal Dominant 3
Cutis Laxa, Autosomal Recessive, Type Iic Cutis Laxa, Autosomal Recessive, Type Iid
Autosomal Recessive Cutis Laxa Type Iii Autosomal Recessive Cutis Laxa Type I
Atp6v0a2-Related Cutis Laxa Efemp2-Related Cutis Laxa
Fbln5-Related Cutis Laxa Ltbp4-Related Cutis Laxa
Acquired Cutis Laxa Autosomal Recessive Cutis Laxa Type 2

Diseases related to Cutis Laxa, Autosomal Recessive, Type Iia via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 31)
# Related Disease Score Top Affiliating Genes
1 cutis laxa, autosomal dominant 1 31.1 FBLN5 EFEMP2 ALDH18A1
2 autosomal recessive cutis laxa type ii classic type 28.7 RIN2 PYCR1 LTBP4 GORAB FBLN5 EFEMP2
3 cutis laxa, autosomal recessive, type iib 28.3 RIN2 PYCR1 LTBP4 GORAB FBLN5 EFEMP2
4 cutis laxa, autosomal recessive, type ia 28.3 RIN2 PYCR1 LTBP4 GORAB FBLN5 EFEMP2
5 cutis laxa 26.8 RIN2 PYCR1 LTBP4 GORAB FBLN5 EFEMP2
6 atp6v0a2-related cutis laxa 11.7
7 autosomal recessive cutis laxa type 2 11.6
8 dandy-walker syndrome 10.3
9 inguinal hernia 10.3
10 myopia 10.3
11 congenital disorders of n-linked glycosylation and multiple pathway 10.2
12 ehlers-danlos syndrome 10.2
13 wrinkly skin syndrome 10.2
14 fbln5-related cutis laxa 10.2
15 geroderma osteodysplasticum 10.0 PYCR1 GORAB
16 ureteric orifice cancer 9.8 FBLN5 EFEMP2
17 tricuspid valve prolapse 9.8 FBLN5 EFEMP2
18 doyne honeycomb retinal dystrophy 9.8 FBLN5 EFEMP2
19 macs syndrome 9.8 RIN2 FBLN5
20 congenital disorder of glycosylation, type in 9.7 GORAB ATP6V0A2
21 supravalvular aortic stenosis 9.7 FBLN5 EFEMP2
22 aortic aneurysm, familial thoracic 1 9.3 LTBP4 FBLN5 EFEMP2
23 loeys-dietz syndrome 9.2 LTBP4 FBLN5 EFEMP2
24 cutis laxa, autosomal recessive, type iiia 9.0 PYCR1 LTBP4 GORAB ALDH18A1
25 arterial tortuosity syndrome 9.0 LTBP4 GORAB FBLN5 EFEMP2
26 scoliosis 9.0 RIN2 LTBP4 FBLN5
27 cutis laxa, autosomal recessive, type iiib 8.7 PYCR1 LTBP4 GORAB EFEMP2 ALDH18A1
28 cutis laxa, autosomal recessive, type ib 8.4 LTBP4 GORAB FBLN5 EFEMP2 ATP6V0A2 ALDH18A1
29 autosomal recessive cutis laxa type i 8.1 RIN2 LTBP4 GORAB FBLN5 EFEMP2 ATP6V0A2
30 cutis laxa, autosomal recessive, type ic 8.0 RIN2 LTBP4 GORAB FBLN5 EFEMP2 ATP6V0A2
31 autosomal recessive cutis laxa type iii 7.6 RIN2 PYCR1 LTBP4 GORAB FBLN5 EFEMP2

Graphical network of the top 20 diseases related to Cutis Laxa, Autosomal Recessive, Type Iia:



Diseases related to Cutis Laxa, Autosomal Recessive, Type Iia

Symptoms & Phenotypes for Cutis Laxa, Autosomal Recessive, Type Iia

Human phenotypes related to Cutis Laxa, Autosomal Recessive, Type Iia:

31 (show all 38)
# Description HPO Frequency HPO Source Accession
1 malar flattening 31 HP:0000272
2 low-set ears 31 HP:0000369
3 frontal bossing 31 HP:0002007
4 intellectual disability 31 HP:0001249
5 seizures 31 HP:0001250
6 failure to thrive 31 HP:0001508
7 scoliosis 31 HP:0002650
8 high palate 31 HP:0000218
9 muscular hypotonia 31 HP:0001252
10 inguinal hernia 31 HP:0000023
11 carious teeth 31 HP:0000670
12 pes planus 31 HP:0001763
13 short nose 31 HP:0003196
14 downslanted palpebral fissures 31 HP:0000494
15 intrauterine growth retardation 31 HP:0001511
16 microcephaly 31 HP:0000252
17 anteverted nares 31 HP:0000463
18 coarse hair 31 HP:0002208
19 feeding difficulties in infancy 31 HP:0008872
20 midface retrusion 31 HP:0011800
21 long philtrum 31 HP:0000343
22 generalized hypotonia 31 HP:0001290
23 strabismus 31 HP:0000486
24 narrow mouth 31 HP:0000160
25 flat face 31 HP:0012368
26 myopia 31 HP:0000545
27 lipodystrophy 31 HP:0009125
28 motor delay 31 HP:0001270
29 congenital hip dislocation 31 HP:0001374
30 dandy-walker malformation 31 HP:0001305
31 joint hypermobility 31 HP:0001382
32 redundant skin 31 HP:0001582
33 wide anterior fontanel 31 HP:0000260
34 polymicrogyria 31 HP:0002126
35 pachygyria 31 HP:0001302
36 brittle hair 31 HP:0002299
37 cutis laxa 31 HP:0000973
38 abnormal isoelectric focusing of serum transferrin 31 HP:0003160

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Ears:
low-set ears

Growth Other:
failure to thrive
intrauterine growth retardation (iugr)

Head And Neck Head:
microcephaly

Head And Neck Face:
long philtrum
flat face
midface hypoplasia

Muscle Soft Tissue:
lipodystrophy
hypotonia
abnormal distribution of subcutaneous fat

Skin Nails Hair Skin:
cutis laxa
loose redundant skin
excessive skin folds

Head And Neck Mouth:
high-arched palate
small mouth

Skeletal:
joint hyperextensibility

Abdomen Gastrointestinal:
feeding problems in infancy

Neurologic Central Nervous System:
seizures
dandy-walker malformation
polymicrogyria
hypotonia
delayed motor development
more
Head And Neck Nose:
short nose
anteverted nares

Skin Nails Hair Hair:
coarse hair
sparse, brittle hair

Head And Neck Eyes:
strabismus
myopia
downslanting palpebral fissures

Skeletal Pelvis:
congenital hip dislocation

Laboratory Abnormalities:
abnormal isoelectric focusing of serum transferrin
defect in n- and o-glycosylation

Skeletal Skull:
large anterior fontanel
delayed closure of the fontanel

Head And Neck Teeth:
dental caries

Skin Nails Hair Skin Histology:
abnormal, broken, shortened elastic fibers
decreased amount of elastin

Clinical features from OMIM:

219200

UMLS symptoms related to Cutis Laxa, Autosomal Recessive, Type Iia:


seizures

MGI Mouse Phenotypes related to Cutis Laxa, Autosomal Recessive, Type Iia:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 integument MP:0010771 9.43 ALDH18A1 ATP6V0A2 EFEMP2 FBLN5 GORAB LTBP4
2 respiratory system MP:0005388 8.92 EFEMP2 FBLN5 GORAB LTBP4

Drugs & Therapeutics for Cutis Laxa, Autosomal Recessive, Type Iia

Search Clinical Trials , NIH Clinical Center for Cutis Laxa, Autosomal Recessive, Type Iia

Genetic Tests for Cutis Laxa, Autosomal Recessive, Type Iia

Anatomical Context for Cutis Laxa, Autosomal Recessive, Type Iia

MalaCards organs/tissues related to Cutis Laxa, Autosomal Recessive, Type Iia:

40
Skin, Eye, Bone, Brain

Publications for Cutis Laxa, Autosomal Recessive, Type Iia

Articles related to Cutis Laxa, Autosomal Recessive, Type Iia:

(show all 27)
# Title Authors PMID Year
1
Further characterization of ATP6V0A2-related autosomal recessive cutis laxa. 56 6
22773132 2012
2
Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2. 56 6
18157129 2008
3
Defective protein glycosylation in patients with cutis laxa syndrome. 56 6
15657616 2005
4
ATP6V0A2-Related Cutis Laxa 61 6
20301755 2009
5
De Barsy syndrome and ATP6V0A2-CDG. 56
20010974 2010
6
Autosomal recessive cutis laxa syndrome revisited. 56
19401719 2009
7
Type II autosomal recessive cutis laxa: report of another patient and molecular studies concerning three candidate genes. 56
18819152 2008
8
Cobblestone-like brain dysgenesis and altered glycosylation in congenital cutis laxa, Debre type. 56
18716235 2008
9
Defining the phenotype in an autosomal recessive cutis laxa syndrome with a combined congenital defect of glycosylation. 56
17971833 2008
10
Genetic defects in the human glycome. 56
16755287 2006
11
Mutation of the COG complex subunit gene COG7 causes a lethal congenital disorder. 56
15107842 2004
12
Wrinkly skin syndrome and the syndrome of cutis laxa with growth and developmental delay represent the same disorder. 56
10406678 1999
13
Neurological involvement in a child with the wrinkly skin syndrome. 56
9916839 1999
14
Male with type II autosomal recessive cutis laxa. 56
8149651 1994
15
Cutis laxa: a feature of Costello syndrome. 56
7512146 1994
16
Cutis laxa and the Costello syndrome. 56
8411045 1993
17
Syndrome of congenital cutis laxa with ligamentous laxity and delayed development: report of a brother and sister from Turkey. 56
1700609 1990
18
Facial anomalies in congenital cutis laxa with retarded growth and skeletal dysplasia. 56
2929668 1989
19
Congenital cutis laxa with retardation of growth and development. 56
3669050 1987
20
Congenital cutis laxa with retardation of growth and motor development: a recessive disorder of connective tissue with male lethality. 56
2420495 1986
21
Variable clinical presentation of cutis laxa. 56
4064367 1985
22
Cutis laxa with intrauterine growth retardation and hip dislocation in a male. 56
565809 1978
23
Cutis laxa associated with severe intrauterine growth retardation and congenital dislocation of the hip. 56
5579863 1971
24
A Novel ATP6V0A2 Mutation Causing Recessive Cutis Laxa with Unusual Manifestations of Bleeding Diathesis and Defective Wound Healing 61
30474613 2019
25
[Clinical and genetic analysis of a patient with cutis laxa]. 61
29419872 2018
26
Discriminative Features in Three Autosomal Recessive Cutis Laxa Syndromes: Cutis Laxa IIA, Cutis Laxa IIB, and Geroderma Osteoplastica. 61
28294978 2017
27
Autosomal recessive cutis laxa type 2A (ARCL2A) mimicking Ehlers-Danlos syndrome by its dermatological manifestations: report of three affected patients. 61
24478233 2014

Variations for Cutis Laxa, Autosomal Recessive, Type Iia

ClinVar genetic disease variations for Cutis Laxa, Autosomal Recessive, Type Iia:

6 (show all 17) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ATP6V0A2 NM_012463.4(ATP6V0A2):c.2293C>T (p.Gln765Ter)SNV Pathogenic 844 rs80356758 12:124239084-124239084 12:123754537-123754537
2 ATP6V0A2 NM_012463.4(ATP6V0A2):c.187C>T (p.Arg63Ter)SNV Pathogenic 845 rs80356750 12:124203239-124203239 12:123718692-123718692
3 ATP6V0A2 NM_012463.4(ATP6V0A2):c.1324G>T (p.Glu442Ter)SNV Pathogenic 21494 rs80356755 12:124228882-124228882 12:123744335-123744335
4 ATP6V0A2 NM_012463.4(ATP6V0A2):c.294+1G>ASNV Pathogenic 21499 rs80356751 12:124206996-124206996 12:123722449-123722449
5 ATP6V0A2 NM_012463.4(ATP6V0A2):c.353_354del (p.Leu118fs)deletion Pathogenic 21500 rs80356752 12:124209259-124209260 12:123724712-123724713
6 ATP6V0A2 NM_012463.4(ATP6V0A2):c.732-2A>GSNV Pathogenic 21501 rs80356753 12:124220076-124220076 12:123735529-123735529
7 ATP6V0A2 NM_012463.4(ATP6V0A2):c.840del (p.Glu281fs)deletion Pathogenic 21502 rs80356754 12:124221619-124221619 12:123737072-123737072
8 ATP6V0A2 NM_012463.4(ATP6V0A2):c.2356_2362del (p.Gly786fs)deletion Pathogenic 39452 rs1566294545 12:124241423-124241429 12:123756876-123756882
9 ATP6V0A2 ATP6V0A2, 1-BP INS, 100Ainsertion Pathogenic 39453
10 ATP6V0A2 NM_012463.4(ATP6V0A2):c.2176-3_2176-2deldeletion Pathogenic 21496 rs367543007 12:124238964-124238965 12:123754417-123754418
11 ATP6V0A2 NM_012463.4(ATP6V0A2):c.1929del (p.Gln645fs)deletion Pathogenic/Likely pathogenic 21495 rs80356756 12:124233326-124233326 12:123748779-123748779
12 ATP6V0A2 NM_012463.4(ATP6V0A2):c.614C>T (p.Ala205Val)SNV Conflicting interpretations of pathogenicity 307580 rs143802431 12:124212422-124212422 12:123727875-123727875
13 ATP6V0A2 NM_012463.4(ATP6V0A2):c.422G>T (p.Arg141Leu)SNV Uncertain significance 390767 rs143509747 12:124209328-124209328 12:123724781-123724781
14 ATP6V0A2 NM_012463.4(ATP6V0A2):c.1018C>T (p.Arg340Trp)SNV Uncertain significance 451817 rs781305219 12:124221798-124221798 12:123737251-123737251
15 ATP6V0A2 NM_012463.4(ATP6V0A2):c.309G>T (p.Lys103Asn)SNV Uncertain significance 307578 rs144499089 12:124209215-124209215 12:123724668-123724668
16 ATP6V0A2 NM_012463.4(ATP6V0A2):c.2302G>A (p.Asp768Asn)SNV Benign 21497 rs367543008 12:124241370-124241370 12:123756823-123756823
17 ATP6V0A2 NM_012463.4(ATP6V0A2):c.*115C>TSNV Benign 21498 rs367543009 12:124242694-124242694 12:123758147-123758147

Expression for Cutis Laxa, Autosomal Recessive, Type Iia

Search GEO for disease gene expression data for Cutis Laxa, Autosomal Recessive, Type Iia.

Pathways for Cutis Laxa, Autosomal Recessive, Type Iia

GO Terms for Cutis Laxa, Autosomal Recessive, Type Iia

Cellular components related to Cutis Laxa, Autosomal Recessive, Type Iia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 collagen-containing extracellular matrix GO:0062023 8.8 LTBP4 FBLN5 EFEMP2

Biological processes related to Cutis Laxa, Autosomal Recessive, Type Iia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of cell growth GO:0001558 9.32 LTBP4 FBLN5
2 cellular amino acid biosynthetic process GO:0008652 9.26 PYCR1 ALDH18A1
3 elastic fiber assembly GO:0048251 9.16 FBLN5 EFEMP2
4 L-proline biosynthetic process GO:0055129 8.96 PYCR1 ALDH18A1
5 proline biosynthetic process GO:0006561 8.62 PYCR1 ALDH18A1

Sources for Cutis Laxa, Autosomal Recessive, Type Iia

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9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
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