ADCL3
MCID: CTS041
MIFTS: 27

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 : 76 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, is also known as adcl3. An important gene associated with Cutis Laxa, Autosomal Dominant 3 is ALDH18A1 (Aldehyde Dehydrogenase 18 Family Member A1). Affiliated tissues include skin, bone and eye, 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 : 58 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)

Symptoms & Phenotypes for Cutis Laxa, Autosomal Dominant 3

Human phenotypes related to Cutis Laxa, Autosomal Dominant 3:

33 (show all 28)
# Description HPO Frequency HPO Source Accession
1 osteopenia 33 occasional (7.5%) HP:0000938
2 strabismus 33 occasional (7.5%) HP:0000486
3 wormian bones 33 occasional (7.5%) HP:0002645
4 talipes equinovarus 33 occasional (7.5%) HP:0001762
5 autistic behavior 33 occasional (7.5%) HP:0000729
6 unilateral renal agenesis 33 occasional (7.5%) HP:0000122
7 aortic regurgitation 33 occasional (7.5%) HP:0001659
8 small foramen magnum 33 occasional (7.5%) HP:0002677
9 low-set ears 33 HP:0000369
10 global developmental delay 33 HP:0001263
11 corneal opacity 33 HP:0007957
12 microcephaly 33 HP:0000252
13 prominent forehead 33 HP:0011220
14 feeding difficulties 33 HP:0011968
15 hernia 33 HP:0100790
16 intrauterine growth retardation 33 HP:0001511
17 protruding ear 33 HP:0000411
18 hip dislocation 33 HP:0002827
19 broad forehead 33 HP:0000337
20 adducted thumb 33 HP:0001181
21 triangular face 33 HP:0000325
22 generalized hypotonia 33 HP:0001290
23 brisk reflexes 33 HP:0001348
24 delayed cranial suture closure 33 HP:0000270
25 cutis laxa 33 HP:0000973
26 premature skin wrinkling 33 HP:0100678
27 psychomotor retardation 33 HP:0025356
28 developmental cataract 33 HP:0000519

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Ears:
low-set ears
prominent ears

Head And Neck Face:
prominent forehead
broad forehead
triangular face

Prenatal Manifestations:
intrauterine growth retardation

Neurologic Central Nervous System:
brisk reflexes
hypotonia
psychomotor retardation
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)

Head And Neck Head:
microcephaly

Abdomen Gastrointestinal:
feeding difficulties

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 30 ALDH18A1

Anatomical Context for Cutis Laxa, Autosomal Dominant 3

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

42
Skin, Bone, Eye

Publications for Cutis Laxa, Autosomal Dominant 3

Articles related to Cutis Laxa, Autosomal Dominant 3:

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

Variations for Cutis Laxa, Autosomal Dominant 3

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

76
# 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

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

6 (show top 50) (show all 66)
# Gene Variation Type Significance SNP ID Assembly Location
1 ALDH18A1 NM_002860.3(ALDH18A1): c.755G> A (p.Arg252Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs864321670 GRCh38 Chromosome 10, 95633012: 95633012
2 ALDH18A1 NM_002860.3(ALDH18A1): c.755G> A (p.Arg252Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs864321670 GRCh37 Chromosome 10, 97392769: 97392769
3 ALDH18A1 NM_002860.3(ALDH18A1): c.412C> T (p.Arg138Trp) single nucleotide variant Pathogenic rs863225044 GRCh38 Chromosome 10, 95637328: 95637328
4 ALDH18A1 NM_002860.3(ALDH18A1): c.412C> T (p.Arg138Trp) single nucleotide variant Pathogenic rs863225044 GRCh37 Chromosome 10, 97397085: 97397085
5 ALDH18A1 NM_002860.3(ALDH18A1): c.413G> A (p.Arg138Gln) single nucleotide variant Pathogenic rs863225045 GRCh38 Chromosome 10, 95637327: 95637327
6 ALDH18A1 NM_002860.3(ALDH18A1): c.413G> A (p.Arg138Gln) single nucleotide variant Pathogenic rs863225045 GRCh37 Chromosome 10, 97397084: 97397084
7 ALDH18A1 NM_002860.3(ALDH18A1): c.413G> T (p.Arg138Leu) single nucleotide variant Pathogenic rs863225045 GRCh38 Chromosome 10, 95637327: 95637327
8 ALDH18A1 NM_002860.3(ALDH18A1): c.413G> T (p.Arg138Leu) single nucleotide variant Pathogenic rs863225045 GRCh37 Chromosome 10, 97397084: 97397084
9 ALDH18A1 NM_002860.3(ALDH18A1): c.1029T> C (p.Ile343=) single nucleotide variant Benign/Likely benign rs41291566 GRCh38 Chromosome 10, 95627491: 95627491
10 ALDH18A1 NM_002860.3(ALDH18A1): c.1029T> C (p.Ile343=) single nucleotide variant Benign/Likely benign rs41291566 GRCh37 Chromosome 10, 97387248: 97387248
11 ALDH18A1 NM_002860.3(ALDH18A1): c.1308G> A (p.Leu436=) single nucleotide variant Conflicting interpretations of pathogenicity rs144816455 GRCh38 Chromosome 10, 95621190: 95621190
12 ALDH18A1 NM_002860.3(ALDH18A1): c.1308G> A (p.Leu436=) single nucleotide variant Conflicting interpretations of pathogenicity rs144816455 GRCh37 Chromosome 10, 97380947: 97380947
13 ALDH18A1 NM_002860.3(ALDH18A1): c.1329C> T (p.Ile443=) single nucleotide variant Benign/Likely benign rs117709404 GRCh38 Chromosome 10, 95621169: 95621169
14 ALDH18A1 NM_002860.3(ALDH18A1): c.1329C> T (p.Ile443=) single nucleotide variant Benign/Likely benign rs117709404 GRCh37 Chromosome 10, 97380926: 97380926
15 ALDH18A1 NM_002860.3(ALDH18A1): c.492C> T (p.Ala164=) single nucleotide variant Conflicting interpretations of pathogenicity rs150472102 GRCh38 Chromosome 10, 95637159: 95637159
16 ALDH18A1 NM_002860.3(ALDH18A1): c.492C> T (p.Ala164=) single nucleotide variant Conflicting interpretations of pathogenicity rs150472102 GRCh37 Chromosome 10, 97396916: 97396916
17 ALDH18A1 NM_002860.3(ALDH18A1): c.1770C> T (p.Ser590=) single nucleotide variant Benign/Likely benign rs11541780 GRCh37 Chromosome 10, 97373754: 97373754
18 ALDH18A1 NM_002860.3(ALDH18A1): c.1770C> T (p.Ser590=) single nucleotide variant Benign/Likely benign rs11541780 GRCh38 Chromosome 10, 95613997: 95613997
19 ALDH18A1 NM_002860.3(ALDH18A1): c.1115C> A (p.Ser372Tyr) single nucleotide variant Benign/Likely benign rs3765571 GRCh38 Chromosome 10, 95626740: 95626740
20 ALDH18A1 NM_002860.3(ALDH18A1): c.1115C> A (p.Ser372Tyr) single nucleotide variant Benign/Likely benign rs3765571 GRCh37 Chromosome 10, 97386497: 97386497
21 ALDH18A1 NM_002860.3(ALDH18A1): c.2207-3C> T single nucleotide variant Conflicting interpretations of pathogenicity rs149309642 GRCh37 Chromosome 10, 97366703: 97366703
22 ALDH18A1 NM_002860.3(ALDH18A1): c.2207-3C> T single nucleotide variant Conflicting interpretations of pathogenicity rs149309642 GRCh38 Chromosome 10, 95606946: 95606946
23 ALDH18A1 NM_002860.3(ALDH18A1): c.1977C> T (p.Ser659=) single nucleotide variant Benign/Likely benign rs1804934 GRCh37 Chromosome 10, 97371146: 97371146
24 ALDH18A1 NM_002860.3(ALDH18A1): c.1977C> T (p.Ser659=) single nucleotide variant Benign/Likely benign rs1804934 GRCh38 Chromosome 10, 95611389: 95611389
25 ALDH18A1 NM_002860.3(ALDH18A1): c.2232G> A (p.Ser744=) single nucleotide variant Likely benign rs148601288 GRCh37 Chromosome 10, 97366675: 97366675
26 ALDH18A1 NM_002860.3(ALDH18A1): c.2232G> A (p.Ser744=) single nucleotide variant Likely benign rs148601288 GRCh38 Chromosome 10, 95606918: 95606918
27 ALDH18A1 NM_002860.3(ALDH18A1): c.2160C> T (p.Phe720=) single nucleotide variant Conflicting interpretations of pathogenicity rs374052426 GRCh37 Chromosome 10, 97370000: 97370000
28 ALDH18A1 NM_002860.3(ALDH18A1): c.2160C> T (p.Phe720=) single nucleotide variant Conflicting interpretations of pathogenicity rs374052426 GRCh38 Chromosome 10, 95610243: 95610243
29 ALDH18A1 NM_002860.3(ALDH18A1): c.1867G> A (p.Asp623Asn) single nucleotide variant Uncertain significance rs770815414 GRCh37 Chromosome 10, 97373555: 97373555
30 ALDH18A1 NM_002860.3(ALDH18A1): c.1867G> A (p.Asp623Asn) single nucleotide variant Uncertain significance rs770815414 GRCh38 Chromosome 10, 95613798: 95613798
31 ALDH18A1 NM_002860.3(ALDH18A1): c.1942C> T (p.Pro648Ser) single nucleotide variant not provided rs768964431 GRCh37 Chromosome 10, 97371181: 97371181
32 ALDH18A1 NM_002860.3(ALDH18A1): c.1942C> T (p.Pro648Ser) single nucleotide variant not provided rs768964431 GRCh38 Chromosome 10, 95611424: 95611424
33 ALDH18A1 NM_002860.3(ALDH18A1): c.1568C> T (p.Ala523Val) single nucleotide variant Uncertain significance rs529294368 GRCh37 Chromosome 10, 97376271: 97376271
34 ALDH18A1 NM_002860.3(ALDH18A1): c.1568C> T (p.Ala523Val) single nucleotide variant Uncertain significance rs529294368 GRCh38 Chromosome 10, 95616514: 95616514
35 ALDH18A1 NM_002860.3(ALDH18A1): c.551C> T (p.Ala184Val) single nucleotide variant Uncertain significance rs201428777 GRCh37 Chromosome 10, 97396857: 97396857
36 ALDH18A1 NM_002860.3(ALDH18A1): c.551C> T (p.Ala184Val) single nucleotide variant Uncertain significance rs201428777 GRCh38 Chromosome 10, 95637100: 95637100
37 ALDH18A1 NM_002860.3(ALDH18A1): c.1777A> G (p.Ser593Gly) single nucleotide variant Uncertain significance rs1231068982 GRCh37 Chromosome 10, 97373747: 97373747
38 ALDH18A1 NM_002860.3(ALDH18A1): c.1777A> G (p.Ser593Gly) single nucleotide variant Uncertain significance rs1231068982 GRCh38 Chromosome 10, 95613990: 95613990
39 ALDH18A1 NM_002860.3(ALDH18A1): c.868G> A (p.Gly290Arg) single nucleotide variant Uncertain significance rs368147360 GRCh37 Chromosome 10, 97388190: 97388190
40 ALDH18A1 NM_002860.3(ALDH18A1): c.868G> A (p.Gly290Arg) single nucleotide variant Uncertain significance rs368147360 GRCh38 Chromosome 10, 95628433: 95628433
41 ALDH18A1 NM_002860.3(ALDH18A1): c.1264C> G (p.Leu422Val) single nucleotide variant Uncertain significance rs142712849 GRCh37 Chromosome 10, 97380991: 97380991
42 ALDH18A1 NM_002860.3(ALDH18A1): c.1264C> G (p.Leu422Val) single nucleotide variant Uncertain significance rs142712849 GRCh38 Chromosome 10, 95621234: 95621234
43 ALDH18A1 NM_002860.3(ALDH18A1): c.1015G> A (p.Val339Ile) single nucleotide variant Uncertain significance rs1346763871 GRCh37 Chromosome 10, 97387262: 97387262
44 ALDH18A1 NM_002860.3(ALDH18A1): c.1015G> A (p.Val339Ile) single nucleotide variant Uncertain significance rs1346763871 GRCh38 Chromosome 10, 95627505: 95627505
45 ALDH18A1 NM_002860.3(ALDH18A1): c.678C> T (p.Val226=) single nucleotide variant Likely benign rs772829720 GRCh37 Chromosome 10, 97393287: 97393287
46 ALDH18A1 NM_002860.3(ALDH18A1): c.678C> T (p.Val226=) single nucleotide variant Likely benign rs772829720 GRCh38 Chromosome 10, 95633530: 95633530
47 ALDH18A1 NM_002860.3(ALDH18A1): c.1604T> A (p.Leu535Gln) single nucleotide variant Uncertain significance rs200452017 GRCh37 Chromosome 10, 97376235: 97376235
48 ALDH18A1 NM_002860.3(ALDH18A1): c.1604T> A (p.Leu535Gln) single nucleotide variant Uncertain significance rs200452017 GRCh38 Chromosome 10, 95616478: 95616478
49 ALDH18A1 NM_002860.3(ALDH18A1): c.428C> T (p.Ser143Leu) single nucleotide variant Uncertain significance GRCh37 Chromosome 10, 97397069: 97397069
50 ALDH18A1 NM_002860.3(ALDH18A1): c.428C> T (p.Ser143Leu) single nucleotide variant Uncertain significance GRCh38 Chromosome 10, 95637312: 95637312

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

Sources for Cutis Laxa, Autosomal Dominant 3

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