ADCL3
MCID: CTS041
MIFTS: 38

Cutis Laxa, Autosomal Dominant 3 (ADCL3)

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 Dominant 3

Summaries for Cutis Laxa, Autosomal Dominant 3

UniProtKB/Swiss-Prot : 73 Cutis laxa, autosomal dominant, 3: A form of cutis laxa, a connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. Additional variable clinical features are gastrointestinal diverticula, hernia, and genital prolapse. Rare manifestations are pulmonary artery stenosis, aortic aneurysm, bronchiectasis, and emphysema. ADCL3 patients manifest thin skin with visible veins and wrinkles, cataract or corneal clouding, moderate intellectual disability, muscular hypotonia with brisk muscle reflexes, clenched fingers, and pre- and postnatal growth retardation.

MalaCards based summary : Cutis Laxa, Autosomal Dominant 3, also known as adcl3, is related to cutis laxa, autosomal dominant 2 and atypical glycine encephalopathy. An important gene associated with Cutis Laxa, Autosomal Dominant 3 is ALDH18A1 (Aldehyde Dehydrogenase 18 Family Member A1), and among its related pathways/superpathways are Metabolism and Carbon metabolism. Affiliated tissues include skin and bone, and related phenotypes are osteopenia and strabismus

Disease Ontology : 12 An autosomal dominant cutis laxa characterized by thin skin with visible veins and wrinkles, cataract or corneal clouding, clenched fingers, pre- and postnatal growth retardation, moderate intellectual disability, and a combination of muscle hypotonia with brisk muscle reflexes that has material basis in heterozygous mutation in the ALDH18A1 gene on chromosome 10q24.

OMIM : 56 Autosomal dominant cutis laxa-3 is characterized by thin skin with visible veins and wrinkles, cataract or corneal clouding, clenched fingers, pre- and postnatal growth retardation, and moderate intellectual disability. In addition, patients exhibit a combination of muscular hypotonia with brisk muscle reflexes (Fischer-Zirnsak et al., 2015). For a general phenotypic description and discussion of genetic heterogeneity of autosomal dominant cutis laxa, see ARCL1 (123700). (616603)

Related Diseases for Cutis Laxa, Autosomal Dominant 3

Graphical network of the top 20 diseases related to Cutis Laxa, Autosomal Dominant 3:



Diseases related to Cutis Laxa, Autosomal Dominant 3

Symptoms & Phenotypes for Cutis Laxa, Autosomal Dominant 3

Human phenotypes related to Cutis Laxa, Autosomal Dominant 3:

31 (show all 29)
# Description HPO Frequency HPO Source Accession
1 osteopenia 31 occasional (7.5%) HP:0000938
2 strabismus 31 occasional (7.5%) HP:0000486
3 wormian bones 31 occasional (7.5%) HP:0002645
4 talipes equinovarus 31 occasional (7.5%) HP:0001762
5 autistic behavior 31 occasional (7.5%) HP:0000729
6 unilateral renal agenesis 31 occasional (7.5%) HP:0000122
7 aortic regurgitation 31 occasional (7.5%) HP:0001659
8 small foramen magnum 31 occasional (7.5%) HP:0002677
9 low-set ears 31 HP:0000369
10 global developmental delay 31 HP:0001263
11 corneal opacity 31 HP:0007957
12 feeding difficulties 31 HP:0011968
13 intrauterine growth retardation 31 HP:0001511
14 microcephaly 31 HP:0000252
15 prominent forehead 31 HP:0011220
16 protruding ear 31 HP:0000411
17 generalized hypotonia 31 HP:0001290
18 hernia 31 HP:0100790
19 postnatal growth retardation 31 HP:0008897
20 hip dislocation 31 HP:0002827
21 broad forehead 31 HP:0000337
22 developmental cataract 31 HP:0000519
23 adducted thumb 31 HP:0001181
24 triangular face 31 HP:0000325
25 delayed cranial suture closure 31 HP:0000270
26 brisk reflexes 31 HP:0001348
27 cutis laxa 31 HP:0000973
28 premature skin wrinkling 31 HP:0100678
29 psychomotor retardation 31 HP:0025356

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Ears:
low-set ears
prominent ears

Prenatal Manifestations:
intrauterine growth retardation

Head And Neck Face:
prominent forehead
broad forehead
triangular face

Neurologic Central Nervous System:
brisk reflexes
psychomotor retardation
hypotonia
cranial vessel tortuosity
foramen magnum stenosis (in some patients)

Skeletal Hands:
adducted thumbs
clenched fingers

Abdomen External Features:
hernias

Skeletal Feet:
clubfoot (in some patients)
pes calcaneovalgus (rare)

Skeletal Skull:
delayed closure of fontanels
wormian bones (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
autism spectrum disorder (rare)

Cardiovascular Heart:
thin, translucent aortic valve (rare)
aortic insufficiency (rare)

Laboratory Abnormalities:
decreased ornithine levels (in some patients)
decreased arginine levels (in some patients)
decreased proline levels (in some patients)

Abdomen Gastrointestinal:
feeding difficulties

Head And Neck Head:
microcephaly

Skeletal Pelvis:
hip dislocation

Head And Neck Eyes:
corneal clouding
strabismus (in some patients)
congenital cataracts

Skeletal Limbs:
joint hyperlaxity

Skeletal:
osteopenia (in some patients)

Skin Nails Hair Skin:
thin, translucent skin
wrinkled skin
lax skin

Genitourinary Kidneys:
unilateral renal agenesis (rare)

Growth Other:
prenatal and postnatal growth retardation

Skeletal Spine:
abnormal spine curvature (in some patients)

Clinical features from OMIM:

616603

Drugs & Therapeutics for Cutis Laxa, Autosomal Dominant 3

Search Clinical Trials , NIH Clinical Center for Cutis Laxa, Autosomal Dominant 3

Genetic Tests for Cutis Laxa, Autosomal Dominant 3

Genetic tests related to Cutis Laxa, Autosomal Dominant 3:

# Genetic test Affiliating Genes
1 Cutis Laxa, Autosomal Dominant 3 29 ALDH18A1

Anatomical Context for Cutis Laxa, Autosomal Dominant 3

MalaCards organs/tissues related to Cutis Laxa, Autosomal Dominant 3:

40
Skin, Bone

Publications for Cutis Laxa, Autosomal Dominant 3

Articles related to Cutis Laxa, Autosomal Dominant 3:

# Title Authors PMID Year
1
Recurrent De Novo Mutations Affecting Residue Arg138 of Pyrroline-5-Carboxylate Synthase Cause a Progeroid Form of Autosomal-Dominant Cutis Laxa. 56 6
26320891 2015
2
New lethal disease involving type I and III collagen defect resembling geroderma osteodysplastica, De Barsy syndrome, and Ehlers-Danlos syndrome IV. 6 56
9643297 1998

Variations for Cutis Laxa, Autosomal Dominant 3

ClinVar genetic disease variations for Cutis Laxa, Autosomal Dominant 3:

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# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ALDH18A1 NM_002860.4(ALDH18A1):c.412C>T (p.Arg138Trp)SNV Pathogenic 217259 rs863225044 10:97397085-97397085 10:95637328-95637328
2 ALDH18A1 NM_002860.4(ALDH18A1):c.413G>A (p.Arg138Gln)SNV Pathogenic 217260 rs863225045 10:97397084-97397084 10:95637327-95637327
3 ALDH18A1 NM_002860.4(ALDH18A1):c.413G>T (p.Arg138Leu)SNV Pathogenic 217261 rs863225045 10:97397084-97397084 10:95637327-95637327
4 ALDH18A1 NM_002860.4(ALDH18A1):c.88+1G>ASNV Likely pathogenic 659530 10:97413046-97413046 10:95653289-95653289
5 ALDH18A1 NM_002860.4(ALDH18A1):c.2160C>T (p.Phe720=)SNV Conflicting interpretations of pathogenicity 392692 rs374052426 10:97370000-97370000 10:95610243-95610243
6 ALDH18A1 NM_002860.4(ALDH18A1):c.1308G>A (p.Leu436=)SNV Conflicting interpretations of pathogenicity 301768 rs144816455 10:97380947-97380947 10:95621190-95621190
7 ALDH18A1 NM_002860.4(ALDH18A1):c.492C>T (p.Ala164=)SNV Conflicting interpretations of pathogenicity 301775 rs150472102 10:97396916-97396916 10:95637159-95637159
8 ALDH18A1 NM_002860.4(ALDH18A1):c.2207-3C>TSNV Conflicting interpretations of pathogenicity 301756 rs149309642 10:97366703-97366703 10:95606946-95606946
9 ALDH18A1 NM_002860.4(ALDH18A1):c.755G>A (p.Arg252Gln)SNV Conflicting interpretations of pathogenicity 217117 rs864321670 10:97392769-97392769 10:95633012-95633012
10 ALDH18A1 NM_002860.4(ALDH18A1):c.1568C>T (p.Ala523Val)SNV Uncertain significance 464039 rs529294368 10:97376271-97376271 10:95616514-95616514
11 ALDH18A1 NM_002860.4(ALDH18A1):c.551C>T (p.Ala184Val)SNV Uncertain significance 464042 rs201428777 10:97396857-97396857 10:95637100-95637100
12 ALDH18A1 NM_002860.4(ALDH18A1):c.1777A>G (p.Ser593Gly)SNV Uncertain significance 464040 rs1231068982 10:97373747-97373747 10:95613990-95613990
13 ALDH18A1 NM_002860.4(ALDH18A1):c.868G>A (p.Gly290Arg)SNV Uncertain significance 464043 rs368147360 10:97388190-97388190 10:95628433-95628433
14 ALDH18A1 NM_002860.4(ALDH18A1):c.1264C>G (p.Leu422Val)SNV Uncertain significance 464038 rs142712849 10:97380991-97380991 10:95621234-95621234
15 ALDH18A1 NM_002860.4(ALDH18A1):c.1015G>A (p.Val339Ile)SNV Uncertain significance 464037 rs1346763871 10:97387262-97387262 10:95627505-95627505
16 ALDH18A1 NM_002860.4(ALDH18A1):c.1604T>A (p.Leu535Gln)SNV Uncertain significance 532701 rs200452017 10:97376235-97376235 10:95616478-95616478
17 ALDH18A1 NM_002860.4(ALDH18A1):c.428C>T (p.Ser143Leu)SNV Uncertain significance 581031 rs1302919102 10:97397069-97397069 10:95637312-95637312
18 ALDH18A1 NM_002860.4(ALDH18A1):c.1393G>C (p.Glu465Gln)SNV Uncertain significance 579657 10:97380862-97380862 10:95621105-95621105
19 ALDH18A1 NM_002860.4(ALDH18A1):c.2231C>T (p.Ser744Leu)SNV Uncertain significance 581547 10:97366676-97366676 10:95606919-95606919
20 ALDH18A1 NM_002860.4(ALDH18A1):c.1233G>T (p.Leu411Phe)SNV Uncertain significance 578899 10:97385132-97385132 10:95625375-95625375
21 ALDH18A1 NM_002860.4(ALDH18A1):c.1078+4A>GSNV Uncertain significance 578302 rs1566018543 10:97387195-97387195 10:95627438-95627438
22 ALDH18A1 NM_002860.4(ALDH18A1):c.709G>C (p.Gly237Arg)SNV Uncertain significance 573157 10:97393256-97393256 10:95633499-95633499
23 ALDH18A1 NM_002860.4(ALDH18A1):c.598C>T (p.Arg200Cys)SNV Uncertain significance 570966 10:97393367-97393367 10:95633610-95633610
24 ALDH18A1 NM_002860.4(ALDH18A1):c.1370G>A (p.Arg457His)SNV Uncertain significance 575749 10:97380885-97380885 10:95621128-95621128
25 ALDH18A1 NM_002860.4(ALDH18A1):c.847C>T (p.Leu283Phe)SNV Uncertain significance 566189 10:97388211-97388211 10:95628454-95628454
26 ALDH18A1 NM_002860.4(ALDH18A1):c.2383A>G (p.Asn795Asp)SNV Uncertain significance 665168 10:97366524-97366524 10:95606767-95606767
27 ALDH18A1 NM_002860.4(ALDH18A1):c.2276C>T (p.Thr759Ile)SNV Uncertain significance 664573 10:97366631-97366631 10:95606874-95606874
28 ALDH18A1 NM_002860.4(ALDH18A1):c.2077A>G (p.Ser693Gly)SNV Uncertain significance 658085 10:97371046-97371046 10:95611289-95611289
29 ALDH18A1 NM_002860.4(ALDH18A1):c.1865G>A (p.Arg622Gln)SNV Uncertain significance 658959 10:97373557-97373557 10:95613800-95613800
30 ALDH18A1 NM_002860.4(ALDH18A1):c.1237G>A (p.Glu413Lys)SNV Uncertain significance 647291 10:97385128-97385128 10:95625371-95625371
31 ALDH18A1 NM_002860.4(ALDH18A1):c.709G>T (p.Gly237Trp)SNV Uncertain significance 638826 10:97393256-97393256 10:95633499-95633499
32 ALDH18A1 NM_002860.4(ALDH18A1):c.169C>A (p.His57Asn)SNV Uncertain significance 660899 10:97402883-97402883 10:95643126-95643126
33 ALDH18A1 NM_002860.4(ALDH18A1):c.1867G>A (p.Asp623Asn)SNV Uncertain significance 424961 rs770815414 10:97373555-97373555 10:95613798-95613798
34 ALDH18A1 NM_002860.4(ALDH18A1):c.678C>T (p.Val226=)SNV Likely benign 464041 rs772829720 10:97393287-97393287 10:95633530-95633530
35 ALDH18A1 NM_002860.4(ALDH18A1):c.2232G>A (p.Ser744=)SNV Likely benign 391463 rs148601288 10:97366675-97366675 10:95606918-95606918
36 ALDH18A1 NM_002860.4(ALDH18A1):c.1977C>T (p.Ser659=)SNV Benign/Likely benign 301761 rs1804934 10:97371146-97371146 10:95611389-95611389
37 ALDH18A1 NM_002860.4(ALDH18A1):c.1770C>T (p.Ser590=)SNV Benign/Likely benign 301762 rs11541780 10:97373754-97373754 10:95613997-95613997
38 ALDH18A1 NM_002860.4(ALDH18A1):c.1115C>A (p.Ser372Tyr)SNV Benign/Likely benign 301770 rs3765571 10:97386497-97386497 10:95626740-95626740
39 ALDH18A1 NM_002860.4(ALDH18A1):c.1329C>T (p.Ile443=)SNV Benign/Likely benign 301767 rs117709404 10:97380926-97380926 10:95621169-95621169
40 ALDH18A1 NM_002860.4(ALDH18A1):c.1029T>C (p.Ile343=)SNV Benign/Likely benign 258823 rs41291566 10:97387248-97387248 10:95627491-95627491
41 ALDH18A1 NM_002860.4(ALDH18A1):c.1942C>T (p.Pro648Ser)SNV not provided 441102 rs768964431 10:97371181-97371181 10:95611424-95611424

UniProtKB/Swiss-Prot genetic disease variations for Cutis Laxa, Autosomal Dominant 3:

73
# Symbol AA change Variation ID SNP ID
1 ALDH18A1 p.Arg138Leu VAR_075887 rs863225045
2 ALDH18A1 p.Arg138Gln VAR_075888 rs863225045
3 ALDH18A1 p.Arg138Trp VAR_075889 rs863225044

Expression for Cutis Laxa, Autosomal Dominant 3

Search GEO for disease gene expression data for Cutis Laxa, Autosomal Dominant 3.

Pathways for Cutis Laxa, Autosomal Dominant 3

GO Terms for Cutis Laxa, Autosomal Dominant 3

Cellular components related to Cutis Laxa, Autosomal Dominant 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.35 MTHFS MTHFD2L GCSH AMT ALDH18A1
2 mitochondrial matrix GO:0005759 8.92 MTHFS MTHFD2L GCSH AMT

Biological processes related to Cutis Laxa, Autosomal Dominant 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 methylation GO:0032259 9.43 GCSH AMT
2 metabolic process GO:0008152 9.4 MTHFD2L ALDH18A1
3 cellular amino acid biosynthetic process GO:0008652 9.37 MTHFD2L ALDH18A1
4 folic acid metabolic process GO:0046655 9.32 MTHFS MTHFD2L
5 glutamate metabolic process GO:0006536 9.26 MTHFS ALDH18A1
6 tetrahydrofolate interconversion GO:0035999 9.16 MTHFS MTHFD2L
7 glycine decarboxylation via glycine cleavage system GO:0019464 8.96 GCSH AMT
8 glycine catabolic process GO:0006546 8.62 GCSH AMT

Molecular functions related to Cutis Laxa, Autosomal Dominant 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 aminomethyltransferase activity GO:0004047 8.62 GCSH AMT

Sources for Cutis Laxa, Autosomal Dominant 3

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