ARCL2B
MCID: CTS023
MIFTS: 42

Cutis Laxa, Autosomal Recessive, Type Iib (ARCL2B)

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 Iib

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

Name: Cutis Laxa, Autosomal Recessive, Type Iib 56 13 71
Arcl2b 56 12 58 73
Autosomal Recessive Cutis Laxa Type 2b 58 29 6
Cutis Laxa with Progeroid Features 56 52 73
Autosomal Recessive Cutis Laxa Type Iib 12 15
Arcl2, Progeroid Type 12 58
Autosomal Recessive Cutis Laxa Type 2, Progeroid Type 58
Cutis Laxa, Autosomal Recessive, Type 2b 39
Cutis Laxa, Autosomal Recessive Type 2b 52
Cutis Laxa Autosomal Recessive Type Iib 73
Cutis Laxa, Autosomal Recessive, 2b 73
Cl Type Iib 73

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive


HPO:

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


Classifications:

Orphanet: 58  
Rare bone diseases
Rare skin diseases
Inborn errors of metabolism
Developmental anomalies during embryogenesis


Summaries for Cutis Laxa, Autosomal Recessive, Type Iib

OMIM : 56 The phenotype of autosomal recessive cutis laxa type II (ARCL2) includes cutis laxa of variable severity, abnormal growth, developmental delay, and associated skeletal abnormalities (summary by Morava et al., 2009). No specific clinical features distinguish ARCL2A (219200), which includes a glycosylation defect, and ARCL2B, in which abnormal glycosylation has not been reported (Morava et al., 2009; Guernsey et al., 2009). For a phenotypic description and discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100). (612940)

MalaCards based summary : Cutis Laxa, Autosomal Recessive, Type Iib, also known as arcl2b, is related to geroderma osteodysplasticum and cutis laxa, autosomal recessive, type iiib. An important gene associated with Cutis Laxa, Autosomal Recessive, Type Iib is PYCR1 (Pyrroline-5-Carboxylate Reductase 1), and among its related pathways/superpathways are Carbon metabolism and Elastic fibre formation. Affiliated tissues include skin, eye and bone, and related phenotypes are hypotelorism and malar flattening

Disease Ontology : 12 A cutis laxa characterized by progeroid features that has material basis in homozygous or compound heterozygous mutation in the PYCR1 gene on chromosome 17q25.3.

UniProtKB/Swiss-Prot : 73 Cutis laxa, autosomal recessive, 2B: 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. Patients do not manifest metabolic abnormalities.

Related Diseases for Cutis Laxa, Autosomal Recessive, Type Iib

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 Iib via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 27)
# Related Disease Score Top Affiliating Genes
1 geroderma osteodysplasticum 30.6 PYCR1 GORAB
2 cutis laxa, autosomal recessive, type iiib 29.3 PYCR1 LTBP4 GORAB EFEMP2 ALDH18A1
3 cutis laxa, autosomal recessive, type iia 29.2 RIN2 PYCR1 LTBP4 GORAB FBLN5 EFEMP2
4 cutis laxa 27.9 RIN2 PYCR1 LTBP4 GORAB FBLN5 EFEMP2
5 autosomal recessive cutis laxa type iii 27.6 RIN2 PYCR1 LTBP4 GORAB FBLN5 EFEMP2
6 microcephaly 10.3
7 wrinkly skin syndrome 10.2
8 atp6v0a2-related cutis laxa 10.2
9 ltbp4-related cutis laxa 10.2
10 ureteric orifice cancer 9.9 FBLN5 EFEMP2
11 tricuspid valve prolapse 9.9 FBLN5 EFEMP2
12 doyne honeycomb retinal dystrophy 9.8 FBLN5 EFEMP2
13 supravalvular aortic stenosis 9.7 FBLN5 EFEMP2
14 macs syndrome 9.7 RIN2 FBLN5
15 cutis laxa, autosomal dominant 1 9.7 FBLN5 EFEMP2 ALDH18A1
16 aortic aneurysm, familial thoracic 1 9.6 LTBP4 FBLN5 EFEMP2
17 loeys-dietz syndrome 9.6 LTBP4 FBLN5 EFEMP2
18 borderline glaucoma 9.4 PYCR3 PYCR2 PYCR1
19 leukodystrophy, hypomyelinating, 10 9.4 PYCR3 PYCR2 PYCR1
20 arterial tortuosity syndrome 9.4 LTBP4 GORAB FBLN5 EFEMP2
21 scoliosis 9.0 RIN2 LTBP4 FBLN5
22 cutis laxa, autosomal recessive, type ib 8.9 LTBP4 GORAB FBLN5 EFEMP2 ATP6V0A2 ALDH18A1
23 cutis laxa, autosomal recessive, type iiia 8.6 PYCR3 PYCR2 PYCR1 LTBP4 GORAB ALDH18A1
24 autosomal recessive cutis laxa type i 8.4 RIN2 LTBP4 GORAB FBLN5 EFEMP2 ATP6V0A2
25 cutis laxa, autosomal recessive, type ic 8.4 RIN2 LTBP4 GORAB FBLN5 EFEMP2 ATP6V0A2
26 cutis laxa, autosomal recessive, type ia 8.2 RIN2 PYCR1 LTBP4 GORAB FBLN5 EFEMP2
27 autosomal recessive cutis laxa type ii classic type 7.8 RIN2 PYCR2 PYCR1 LTBP4 GORAB FBLN5

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



Diseases related to Cutis Laxa, Autosomal Recessive, Type Iib

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

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

31 (show all 29)
# Description HPO Frequency HPO Source Accession
1 hypotelorism 31 occasional (7.5%) HP:0000601
2 malar flattening 31 HP:0000272
3 hypertelorism 31 HP:0000316
4 agenesis of corpus callosum 31 HP:0001274
5 frontal bossing 31 HP:0002007
6 failure to thrive 31 HP:0001508
7 scoliosis 31 HP:0002650
8 hydrocephalus 31 HP:0000238
9 osteopenia 31 HP:0000938
10 global developmental delay 31 HP:0001263
11 bowing of the long bones 31 HP:0006487
12 downslanted palpebral fissures 31 HP:0000494
13 intrauterine growth retardation 31 HP:0001511
14 microcephaly 31 HP:0000252
15 gastroesophageal reflux 31 HP:0002020
16 midface retrusion 31 HP:0011800
17 prominent forehead 31 HP:0011220
18 protruding ear 31 HP:0000411
19 congenital hip dislocation 31 HP:0001374
20 broad forehead 31 HP:0000337
21 deeply set eye 31 HP:0000490
22 joint hypermobility 31 HP:0001382
23 bulbous nose 31 HP:0000414
24 redundant skin 31 HP:0001582
25 large fontanelles 31 HP:0000239
26 triangular face 31 HP:0000325
27 blue sclerae 31 HP:0000592
28 prominent superficial veins 31 HP:0001015
29 narrow nasal ridge 31 HP:0000418

Symptoms via clinical synopsis from OMIM:

56
Growth Other:
failure to thrive
intrauterine growth retardation
poor postnatal growth

Head And Neck Head:
microcephaly
large fontanel

Skeletal Pelvis:
congenital hip dislocation

Head And Neck Eyes:
blue sclerae
downslanting palpebral fissures (in 2 patients)
hypotelorism (in 2 patients)
deep-set eyes (in 2 patients)

Neurologic Central Nervous System:
developmental delay
agenesis of the corpus callosum (in 2 patients)
hydrocephalus (in 2 patients)

Skeletal Limbs:
bowing of long bones

Cardiovascular Vascular:
no vascular tortuosity

Skeletal Hands:
long digits (in 2 patients)
clasped thumb

Skeletal:
osteopenia
joint hyperextensibility

Abdomen Gastrointestinal:
gastroesophageal reflux

Head And Neck Face:
triangular face
midface hypoplasia
broad, prominent forehead
sagging cheeks
aged appearance

Skin Nails Hair Skin:
cutis laxa
prominent veins
loose redundant skin (especially of dorsum of hands and feet and anterior abdominal wall)
reduced skin elasticity
wrinkly skin

Head And Neck Ears:
prominent ears

Head And Neck Nose:
prominent bulbous nose

Skeletal Spine:
scoliosis (in 2 patients)

Laboratory Abnormalities:
no metabolic abnormalities

Clinical features from OMIM:

612940

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

45
# Description MGI Source Accession Score Top Affiliating Genes
1 integument MP:0010771 9.1 ALDH18A1 ATP6V0A2 EFEMP2 FBLN5 GORAB LTBP4

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

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

Genetic Tests for Cutis Laxa, Autosomal Recessive, Type Iib

Genetic tests related to Cutis Laxa, Autosomal Recessive, Type Iib:

# Genetic test Affiliating Genes
1 Autosomal Recessive Cutis Laxa Type 2b 29 PYCR1

Anatomical Context for Cutis Laxa, Autosomal Recessive, Type Iib

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

40
Skin, Eye, Bone

Publications for Cutis Laxa, Autosomal Recessive, Type Iib

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

# Title Authors PMID Year
1
Mutations in PYCR1 cause cutis laxa with progeroid features. 56 6
19648921 2009
2
Geroderma osteodysplasticum hereditaria and wrinkly skin syndrome in 22 patients from Oman. 56 6
18348262 2008
3
Gerodermia osteodysplastica/wrinkly skin syndrome: report of three patients and brief review of the literature. 56 6
18304158 2008
4
Wrinkly skin syndrome. 56 6
16045708 2005
5
Gerodermia osteodysplastica and wrinkly skin syndrome: are they the same? 56 6
11424136 2001
6
Autosomal recessive cutis laxa syndrome revisited. 56
19401719 2009
7
Mutation in pyrroline-5-carboxylate reductase 1 gene in families with cutis laxa type 2. 56
19576563 2009
8
Discriminative Features in Three Autosomal Recessive Cutis Laxa Syndromes: Cutis Laxa IIA, Cutis Laxa IIB, and Geroderma Osteoplastica. 61
28294978 2017
9
Genotype-phenotype spectrum of PYCR1-related autosomal recessive cutis laxa. 61
24035636 2013
10
The phenotype caused by PYCR1 mutations corresponds to geroderma osteodysplasticum rather than autosomal recessive cutis laxa type 2. 61
21204221 2011

Variations for Cutis Laxa, Autosomal Recessive, Type Iib

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

6 (show all 15) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PYCR1 NM_006907.4(PYCR1):c.797G>A (p.Arg266Gln)SNV Pathogenic 13190 rs121918374 17:79892202-79892202 17:81934326-81934326
2 PYCR1 NM_006907.4(PYCR1):c.616G>T (p.Gly206Trp)SNV Pathogenic 13191 rs121918375 17:79892546-79892546 17:81934670-81934670
3 PYCR1 NM_006907.4(PYCR1):c.618_633+7deldeletion Pathogenic 13192 17:79892522-79892544 17:81934646-81934668
4 PYCR1 PYCR1, 3-BP DEL, NT797+2deletion Pathogenic 13194
5 PYCR1 NM_006907.4(PYCR1):c.11del (p.Gly4fs)deletion Pathogenic 13195 17:79894680-79894680 17:81936804-81936804
6 PYCR1 NM_006907.4(PYCR1):c.355C>G (p.Arg119Gly)SNV Pathogenic 13196 rs121918376 17:79892987-79892987 17:81935111-81935111
7 PYCR1 NM_006907.4(PYCR1):c.356G>A (p.Arg119His)SNV Pathogenic 13197 rs121918377 17:79892986-79892986 17:81935110-81935110
8 PYCR1 NM_006907.4(PYCR1):c.355C>T (p.Arg119Cys)SNV Pathogenic 488456 rs121918376 17:79892987-79892987 17:81935111-81935111
9 PYCR1 NM_006907.4(PYCR1):c.59dup (p.Ala21fs)duplication Pathogenic 488457 rs762218403 17:79894631-79894632 17:81936755-81936756
10 PYCR1 NM_006907.4(PYCR1):c.722C>T (p.Ala241Val)SNV Pathogenic 694719 17:79892277-79892277 17:81934401-81934401
11 PYCR1 NM_006907.4(PYCR1):c.11G>T (p.Gly4Val)SNV Pathogenic 694681 17:79894680-79894680 17:81936804-81936804
12 PYCR1 NM_006907.4(PYCR1):c.540+1G>ASNV Pathogenic 694712 17:79892801-79892801 17:81934925-81934925
13 PYCR1 NM_006907.4(PYCR1):c.535G>A (p.Ala179Thr)SNV Pathogenic/Likely pathogenic 449091 rs139751598 17:79892807-79892807 17:81934931-81934931
14 PYCR1 NM_006907.4(PYCR1):c.866A>G (p.Lys289Arg)SNV Likely pathogenic 800973 17:79891184-79891184 17:81933308-81933308
15 PYCR1 NM_006907.4(PYCR1):c.334C>T (p.Arg112Trp)SNV Conflicting interpretations of pathogenicity 282265 rs147653673 17:79893008-79893008 17:81935132-81935132

UniProtKB/Swiss-Prot genetic disease variations for Cutis Laxa, Autosomal Recessive, Type Iib:

73
# Symbol AA change Variation ID SNP ID
1 PYCR1 p.Arg119Gly VAR_059068 rs121918376
2 PYCR1 p.Arg119His VAR_059069 rs121918377
3 PYCR1 p.Ala179Thr VAR_059070 rs139751598
4 PYCR1 p.Gly206Arg VAR_059072 rs121918375
5 PYCR1 p.Gly206Trp VAR_059073 rs121918375
6 PYCR1 p.Arg266Gln VAR_059076 rs121918374

Expression for Cutis Laxa, Autosomal Recessive, Type Iib

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

Pathways for Cutis Laxa, Autosomal Recessive, Type Iib

GO Terms for Cutis Laxa, Autosomal Recessive, Type Iib

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

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.62 PYCR3 PYCR2 PYCR1 ALDH18A1
2 cellular amino acid biosynthetic process GO:0008652 9.46 PYCR3 PYCR2 PYCR1 ALDH18A1
3 regulation of cell growth GO:0001558 9.37 LTBP4 FBLN5
4 elastic fiber assembly GO:0048251 9.26 FBLN5 EFEMP2
5 L-proline biosynthetic process GO:0055129 9.26 PYCR3 PYCR2 PYCR1 ALDH18A1
6 proline biosynthetic process GO:0006561 8.92 PYCR3 PYCR2 PYCR1 ALDH18A1

Molecular functions related to Cutis Laxa, Autosomal Recessive, Type Iib according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.26 PYCR3 PYCR2 PYCR1 ALDH18A1
2 pyrroline-5-carboxylate reductase activity GO:0004735 8.8 PYCR3 PYCR2 PYCR1

Sources for Cutis Laxa, Autosomal Recessive, Type Iib

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
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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