Cutis Laxa, Autosomal Recessive, Type Iiib disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

OMIM®: ⁵⁷ De Barsy syndrome, also known as autosomal recessive cutis laxa type III (ARCL3), is a rare autosomal recessive disorder characterized by an aged appearance with distinctive facial features, sparse hair, ophthalmologic abnormalities, intrauterine growth retardation (IUGR), and cutis laxa (summary by Lin et al., 2011). For a phenotypic description and a discussion of genetic heterogeneity of de Barsy syndrome, see 219150. For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see 219200. (614438) (Updated 08-Dec-2022)

MalaCards based summary: Cutis Laxa, Autosomal Recessive, Type Iiib, also known as pycr1-related de barsy syndrome, is related to cutis laxa and cutis laxa, autosomal dominant 3. An important gene associated with Cutis Laxa, Autosomal Recessive, Type Iiib is PYCR1 (Pyrroline-5-Carboxylate Reductase 1), and among its related pathways/superpathways are superpathway of L-citrulline metabolism and Amino acid metabolism. Affiliated tissues include skin and eye, and related phenotypes are intellectual disability and osteopenia

UniProtKB/Swiss-Prot: ⁷³ A disorder characterized by an aged appearance with distinctive facial features, sparse hair, ophthalmologic abnormalities, intrauterine growth retardation, and cutis laxa.

Disease Ontology: ¹¹ An autosomal recessive cutis laxa type III that has material basis in homozygous or compound heterozygous mutation in the PYCR1 gene on chromosome 17q25.

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Related Diseases for Cutis Laxa, Autosomal Recessive, Type Iiib

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
Cutis Laxa, Autosomal Recessive, Type Iie	Autosomal Recessive Cutis Laxa Type Iii
Autosomal Recessive Cutis Laxa Type I	Atp6v0a2-Related Cutis Laxa
Efemp2-Related Cutis Laxa	Eln-Related Cutis Laxa
Fbln5-Related Cutis Laxa	Ltbp4-Related Cutis Laxa
Acquired Cutis Laxa

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

(show all 26)

#	Related Disease	Score	Top Affiliating Genes
1	cutis laxa	28.4	RIN2 PYCR1 LTBP4 GORAB EFEMP2 ATP6V0A2
2	cutis laxa, autosomal dominant 3	10.0	PYCR1 ALDH18A1
3	leukodystrophy, hypomyelinating, 10	10.0	PYCR1 ALDH18A1
4	immunodeficiency 47	9.8	PYCR1 ATP6V0A2 ALDH18A1
5	bladder diverticulum	9.7	LTBP4 EFEMP2
6	congenital disorder of glycosylation, type in	9.7	GORAB ATP6V0A2
7	arterial tortuosity syndrome	9.7	LTBP4 EFEMP2
8	geleophysic dysplasia	9.6	LTBP4 EFEMP2
9	supravalvular aortic stenosis	9.6	LTBP4 EFEMP2
10	loeys-dietz syndrome	9.6	LTBP4 EFEMP2
11	diaphragmatic hernia, congenital	9.5	LTBP4 EFEMP2
12	cutis laxa, autosomal recessive, type iid	9.5	RIN2 GORAB ATP6V0A2 ALDH18A1
13	inguinal hernia	9.3	PYCR1 LTBP4 EFEMP2 ATP6V0A2
14	cutis laxa, autosomal recessive, type ia	9.2	LTBP4 EFEMP2 ATP6V0A2 ALDH18A1
15	wrinkly skin syndrome	9.2	PYCR1 GORAB EFEMP2 ATP6V0A2 ALDH18A1
16	cutis laxa, autosomal dominant 1	9.1	PYCR1 LTBP4 EFEMP2 ATP6V0A2 ALDH18A1
17	cutis laxa, autosomal recessive, type iiia	9.0	RIN2 PYCR1 LTBP4 GORAB ATP6V0A2 ALDH18A1
18	cutis laxa, autosomal recessive, type ic	8.8	RIN2 LTBP4 GORAB EFEMP2 ATP6V0A2 ALDH18A1
19	occipital horn syndrome	8.8	RIN2 LTBP4 GORAB EFEMP2 ATP6V0A2 ALDH18A1
20	autosomal recessive cutis laxa type i	8.6	RIN2 PYCR1 LTBP4 GORAB EFEMP2 ATP6V0A2
21	autosomal recessive cutis laxa type iii	8.6	RIN2 PYCR1 LTBP4 GORAB EFEMP2 ATP6V0A2
22	autosomal recessive cutis laxa type ii classic type	8.6	RIN2 PYCR1 LTBP4 GORAB EFEMP2 ATP6V0A2
23	cutis laxa, autosomal recessive, type ib	8.6	RIN2 PYCR1 LTBP4 GORAB EFEMP2 ATP6V0A2
24	cutis laxa, autosomal recessive, type iib	8.6	RIN2 PYCR1 LTBP4 GORAB EFEMP2 ATP6V0A2
25	geroderma osteodysplasticum	8.6	RIN2 PYCR1 LTBP4 GORAB EFEMP2 ATP6V0A2
26	cutis laxa, autosomal recessive, type iia	8.6	RIN2 PYCR1 LTBP4 GORAB EFEMP2 ATP6V0A2

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

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

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

³⁰ (show all 33)

#	Description	HPO Frequency	HPO Source Accession
1	intellectual disability ³⁰	Very rare (1%)	HP:0001249
2	osteopenia ³⁰	Very rare (1%)	HP:0000938
3	cataract ³⁰	Very rare (1%)	HP:0000518
4	inguinal hernia ³⁰	Very rare (1%)	HP:0000023
5	hypertelorism ³⁰	Very rare (1%)	HP:0000316
6	delayed speech and language development ³⁰	Very rare (1%)	HP:0000750
7	pes planus ³⁰	Very rare (1%)	HP:0001763
8	prominent forehead ³⁰	Very rare (1%)	HP:0011220
9	cryptorchidism ³⁰	Very rare (1%)	HP:0000028
10	osteoporosis ³⁰	Very rare (1%)	HP:0000939
11	intrauterine growth retardation ³⁰	Very rare (1%)	HP:0001511
12	elbow flexion contracture ³⁰	Very rare (1%)	HP:0002987
13	deeply set eye ³⁰	Very rare (1%)	HP:0000490
14	fine hair ³⁰	Very rare (1%)	HP:0002213
15	hip dislocation ³⁰	Very rare (1%)	HP:0002827
16	large fontanelles ³⁰	Very rare (1%)	HP:0000239
17	pyloric stenosis ³⁰	Very rare (1%)	HP:0002021
18	thin vermilion border ³⁰	Very rare (1%)	HP:0000233
19	blue sclerae ³⁰	Very rare (1%)	HP:0000592
20	underdeveloped nasal alae ³⁰	Very rare (1%)	HP:0000430
21	sparse hair ³⁰	Very rare (1%)	HP:0008070
22	posteriorly rotated ears ³⁰	Very rare (1%)	HP:0000358
23	athetosis ³⁰	Very rare (1%)	HP:0002305
24	cutis laxa ³⁰	Very rare (1%)	HP:0000973
25	excessive wrinkled skin ³⁰	Very rare (1%)	HP:0007392
26	thin skin ³⁰	Very rare (1%)	HP:0000963
27	developmental glaucoma ³⁰	Very rare (1%)	HP:0001087
28	narrow palpebral fissure ³⁰	Very rare (1%)	HP:0045025
29	dermal translucency ³⁰	Very rare (1%)	HP:0010648
30	prominent superficial veins ³⁰	Very rare (1%)	HP:0001015
31	narrow nasal ridge ³⁰	Very rare (1%)	HP:0000418
32	prominent ear helix ³⁰	Very rare (1%)	HP:0009904
33	triangular face ³⁰		HP:0000325

Symptoms via clinical synopsis from OMIM®:

⁵⁷ (Updated 08-Dec-2022)

Neurologic Central Nervous System:
agenesis of corpus callosum
developmental delay
athetoid movements
impaired intellectual development (variable)

Skeletal:
osteopenia

Genitourinary External Genitalia Male:
inguinal hernia

Head And Neck Face:
prominent forehead
triangular face
prognathism
malar hypoplasia
progeroid appearance

Growth Other:
intrauterine growth retardation

Skeletal Hands:
joint hypermobility
finger contractures

Head And Neck Ears:
dysplastic ears
large ears

Cardiovascular Vascular:
aortic root dilation

Skin Nails Hair Skin:
lax, wrinkled skin
congenital skin wrinkling (esp. dorsum of hands and feet)
prominent cutaneous venous pattern

Skin Nails Hair Skin Electron Microscopy:
marked reduction elastic fiber size

Skeletal Spine:
scoliosis

Head And Neck Eyes:
cataract
glaucoma
blue sclerae
deep-set eyes

Growth Height:
short stature

Genitourinary Internal Genitalia Male:
cryptorchidism

Skeletal Pelvis:
congenital hip dislocation

Skeletal Feet:
joint hypermobility

Head And Neck Mouth:
thin lips

Head And Neck Nose:
pinched nose

Skin Nails Hair Skin Histology:
sparse, thinned and fragmented elastic fibers in reticular dermis

Clinical features from OMIM®:

614438 (Updated 08-Dec-2022)

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

⁴⁵

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	integument	MP:0010771	9.02	ALDH18A1 ATP6V0A2 EFEMP2 GORAB LTBP4

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

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

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Genetic Tests for Cutis Laxa, Autosomal Recessive, Type Iiib

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

#	Genetic test	Affiliating Genes
1	Pycr1-Related De Barsy Syndrome ²⁸	PYCR1

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Anatomical Context for Cutis Laxa, Autosomal Recessive, Type Iiib

Organs/tissues related to Cutis Laxa, Autosomal Recessive, Type Iiib:

MalaCards : Skin, Eye

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Publications for Cutis Laxa, Autosomal Recessive, Type Iiib

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

#	Title	Authors	PMID	Year
1	Compound heterozygous mutations in PYCR1 further expand the phenotypic spectrum of De Barsy syndrome. ⁵⁷ ⁵	Lin DS...Lin SP	22052856	2011
2	Mutations in PYCR1 cause cutis laxa with progeroid features. ⁵⁷ ⁵	Reversade B...Kornak U	19648921	2009
3	De Barsy syndrome--an autosomal recessive, progeroid syndrome. ⁵⁷ ⁵	Kunze J...Riebel T	4076251	1985
4	A Transcriptome Study of Progeroid Neurocutaneous Syndrome Reveals POSTN As a New Element in Proline Metabolic Disorder. ⁶²	Huang YW...Lin DS	30574417	2018
5	Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency. ⁶²	Balasubramaniam S...Christodoulou J	28409271	2017
6	Defect in proline synthesis: pyrroline-5-carboxylate reductase 1 deficiency leads to a complex clinical phenotype with collagen and elastin abnormalities. ⁶²	Kretz R...Haberle J	21487760	2011

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Genes for Cutis Laxa, Autosomal Recessive, Type Iiib

Genes related to Cutis Laxa, Autosomal Recessive, Type Iiib (1 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	PYCR1	Pyrroline-5-Carboxylate Reductase 1	Protein Coding	1657.35	Molecular basis known ⁵⁷ Pathogenic ⁵ Causative germline mutation ⁵⁸ Causative variation ⁷³ Genetic Tests ²⁸ DISEASES inferred ¹⁴	4076251 19648921 22052856
2	ALDH18A1	Aldehyde Dehydrogenase 18 Family Member A1	Protein Coding	7.26	DISEASES inferred ¹⁴
3	GORAB	Golgin, RAB6 Interacting	Protein Coding	7.01	DISEASES inferred ¹⁴
4	ATP6V0A2	ATPase H+ Transporting V0 Subunit A2	Protein Coding	6.84	DISEASES inferred ¹⁴
5	LTBP4	Latent Transforming Growth Factor Beta Binding Protein 4	Protein Coding	6.22	DISEASES inferred ¹⁴
6	EFEMP2	EGF Containing Fibulin Extracellular Matrix Protein 2	Protein Coding	6.17	DISEASES inferred ¹⁴
7	RIN2	Ras And Rab Interactor 2	Protein Coding	6.04	DISEASES inferred ¹⁴

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Variations for Cutis Laxa, Autosomal Recessive, Type Iiib

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

⁵

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	Position
1	PYCR1	NM_006907.4(PYCR1):c.752G>A (p.Arg251His)	SNV	Pathogenic	13198	rs121918378	GRCh37: 17:79892247-79892247 GRCh38: 17:81934371-81934371
2	PYCR1	NM_006907.4(PYCR1):c.769G>A (p.Ala257Thr)	SNV	Pathogenic	29863	rs281875318	GRCh37: 17:79892230-79892230 GRCh38: 17:81934354-81934354
3	PYCR1	NM_006907.4(PYCR1):c.345del (p.Arg116fs)	DEL	Pathogenic	29864	rs758601634	GRCh37: 17:79892997-79892997 GRCh38: 17:81935121-81935121
4	PYCR1	NM_006907.4(PYCR1):c.743G>A (p.Gly248Glu)	SNV	Pathogenic	29865	rs281875319	GRCh37: 17:79892256-79892256 GRCh38: 17:81934380-81934380
5	PYCR1	NM_006907.4(PYCR1):c.356G>A (p.Arg119His)	SNV	Pathogenic	13197	rs121918377	GRCh37: 17:79892986-79892986 GRCh38: 17:81935110-81935110
6	PYCR1	NM_006907.4(PYCR1):c.559G>A (p.Ala187Thr)	SNV	Uncertain Significance	973232	rs763349891	GRCh37: 17:79892603-79892603 GRCh38: 17:81934727-81934727
7	PYCR1	NM_006907.4(PYCR1):c.334C>T (p.Arg112Trp)	SNV	Uncertain Significance	282265	rs147653673	GRCh37: 17:79893008-79893008 GRCh38: 17:81935132-81935132

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

⁷³

#	Symbol	AA change	Variation ID	SNP ID
1	PYCR1	p.Arg251His	VAR_059074	rs121918378
2	PYCR1	p.Ala257Thr	VAR_059075	rs281875318
3	PYCR1	p.Gly248Glu	VAR_067600	rs281875319

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Expression for Cutis Laxa, Autosomal Recessive, Type Iiib

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

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Pathways for Cutis Laxa, Autosomal Recessive, Type Iiib

Pathways related to Cutis Laxa, Autosomal Recessive, Type Iiib according to GeneCards Suite gene sharing:

#	Super pathways	Score	Top Affiliating Genes
1	superpathway of L-citrulline metabolism ⁶¹ Show member pathways citrulline-nitric oxide cycle ⁶¹ Effects of nitric oxide ⁷⁴ L-citrulline biosynthesis ⁶¹ nitric oxide biosynthesis II (mammals) ⁶¹ Nitric oxide metabolism in cystic fibrosis ⁷⁴ urea cycle ⁶¹ Urea cycle ⁶⁶ Urea cycle and associated pathways ⁷⁴ Urea cycle and metabolism of amino groups ⁷⁴	11.24	PYCR1 ALDH18A1
2	Amino acid metabolism ⁷⁴ Show member pathways Amino acid metabolism pathway excerpt: histidine catabolism extension ⁷⁴	11.14	PYCR1 ALDH18A1
3	Elastic fibre formation ⁶⁶ Show member pathways Molecules associated with elastic fibres ⁶⁶	10.86	LTBP4 EFEMP2
4	Glutamate and glutamine metabolism ⁶⁶ Show member pathways L-glutamate and L-glutamine biosynthesis ⁶¹ L-ornithine biosynthesis II ⁶¹ L-proline biosynthesis I ⁶¹ ornithine de novo biosynthesis ⁶¹ proline biosynthesis ⁶¹	10.09	PYCR1 ALDH18A1

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GO Terms for Cutis Laxa, Autosomal Recessive, Type Iiib

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

#	Name	GO ID	Score	Top Affiliating Genes
1	microfibril	GO:0001527	8.92	LTBP4 EFEMP2

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

#	Name	GO ID	Score	Top Affiliating Genes
1	elastic fiber assembly	GO:0048251	9.33	LTBP4 EFEMP2
2	amino acid biosynthetic process	GO:0008652	9.26	PYCR1 ALDH18A1
3	L-proline biosynthetic process	GO:0055129	9.26	PYCR1 ALDH18A1
4	proline biosynthetic process	GO:0006561	8.92	PYCR1 ALDH18A1

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Sources for Cutis Laxa, Autosomal Recessive, Type Iiib

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⁵¹ NIH Clinical Center

⁵² NINDS

⁵³ Novoseek

⁵⁴ Novus Biologicals

⁵⁵ ODiseA

⁵⁶ OMIM via Orphanet

⁵⁷ OMIM® (Updated 08-Dec-2022)

⁵⁸ Orphanet

⁵⁹ PathCards

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⁶⁸ SNOMED-CT

⁶⁹ SNOMED-CT via HPO

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ WikiPathways

⁷⁵ Wikipedia

ARCL3B MCID: CTS032 MIFTS: 39	Cutis Laxa, Autosomal Recessive, Type Iiib (ARCL3B) 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, Respiratory diseases, Skin diseases	Data Licensing For inquiries, contact: [email protected]
Genes Variations Tissues Related diseases Publications Symptoms & Phenotypes Expand all tables

Cutis Laxa, Autosomal Recessive, Type Iiib (ARCL3B)

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

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

Characteristics:

Inheritance:

Classifications:

External Ids:

Summaries for Cutis Laxa, Autosomal Recessive, Type Iiib

Related Diseases for Cutis Laxa, Autosomal Recessive, Type Iiib

Diseases in the Cutis Laxa family:

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

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

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

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

Symptoms via clinical synopsis from OMIM®:

Clinical features from OMIM®:

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

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

Genetic Tests for Cutis Laxa, Autosomal Recessive, Type Iiib

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

Anatomical Context for Cutis Laxa, Autosomal Recessive, Type Iiib

Organs/tissues related to Cutis Laxa, Autosomal Recessive, Type Iiib:

Publications for Cutis Laxa, Autosomal Recessive, Type Iiib

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

Genes for Cutis Laxa, Autosomal Recessive, Type Iiib

Genes related to Cutis Laxa, Autosomal Recessive, Type Iiib (1 elite genes):

Variations for Cutis Laxa, Autosomal Recessive, Type Iiib

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

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

Expression for Cutis Laxa, Autosomal Recessive, Type Iiib

Pathways for Cutis Laxa, Autosomal Recessive, Type Iiib

Pathways related to Cutis Laxa, Autosomal Recessive, Type Iiib according to GeneCards Suite gene sharing:

GO Terms for Cutis Laxa, Autosomal Recessive, Type Iiib

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

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

Sources for Cutis Laxa, Autosomal Recessive, Type Iiib