ADCL3
MCID: CTS041
MIFTS: 26

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 : 75 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 low-set ears and osteopenia

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 : 57 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

Symptoms via clinical synopsis from OMIM:

57
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 Limbs:
joint hyperlaxity

Abdomen External Features:
hernias

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

Genitourinary Kidneys:
unilateral renal agenesis (rare)

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 Hands:
adducted thumbs
clenched fingers

Skeletal:
osteopenia (in some patients)

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

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

Growth Other:
prenatal and postnatal growth retardation

Skeletal Spine:
abnormal spine curvature (in some patients)


Clinical features from OMIM:

616603

Human phenotypes related to Cutis Laxa, Autosomal Dominant 3:

32 (show all 27)
# Description HPO Frequency HPO Source Accession
1 low-set ears 32 HP:0000369
2 osteopenia 32 occasional (7.5%) HP:0000938
3 global developmental delay 32 HP:0001263
4 corneal opacity 32 HP:0007957
5 microcephaly 32 HP:0000252
6 prominent forehead 32 HP:0011220
7 feeding difficulties 32 HP:0011968
8 hernia 32 HP:0100790
9 strabismus 32 occasional (7.5%) HP:0000486
10 wormian bones 32 occasional (7.5%) HP:0002645
11 intrauterine growth retardation 32 HP:0001511
12 protruding ear 32 HP:0000411
13 talipes equinovarus 32 occasional (7.5%) HP:0001762
14 hip dislocation 32 HP:0002827
15 broad forehead 32 HP:0000337
16 adducted thumb 32 HP:0001181
17 triangular face 32 HP:0000325
18 generalized hypotonia 32 HP:0001290
19 brisk reflexes 32 HP:0001348
20 autistic behavior 32 occasional (7.5%) HP:0000729
21 unilateral renal agenesis 32 occasional (7.5%) HP:0000122
22 delayed cranial suture closure 32 HP:0000270
23 aortic regurgitation 32 occasional (7.5%) HP:0001659
24 congenital cataract 32 HP:0000519
25 cutis laxa 32 HP:0000973
26 premature skin wrinkling 32 HP:0100678
27 small foramen magnum 32 occasional (7.5%) HP:0002677

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:

41
Skin, Bone, Eye

Publications for Cutis Laxa, Autosomal Dominant 3

Variations for Cutis Laxa, Autosomal Dominant 3

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

75
# 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 64)
# Gene Variation Type Significance SNP ID Assembly Location
1 ALDH18A1 NM_002860.3(ALDH18A1): c.755G> A (p.Arg252Gln) single nucleotide variant Pathogenic rs864321670 GRCh38 Chromosome 10, 95633012: 95633012
2 ALDH18A1 NM_002860.3(ALDH18A1): c.755G> A (p.Arg252Gln) single nucleotide variant Pathogenic 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 Likely benign rs374052426 GRCh37 Chromosome 10, 97370000: 97370000
28 ALDH18A1 NM_002860.3(ALDH18A1): c.2160C> T (p.Phe720=) single nucleotide variant Likely benign rs374052426 GRCh38 Chromosome 10, 95610243: 95610243
29 ALDH18A1 NM_002860.3(ALDH18A1): c.1942C> T (p.Pro648Ser) single nucleotide variant not provided rs768964431 GRCh37 Chromosome 10, 97371181: 97371181
30 ALDH18A1 NM_002860.3(ALDH18A1): c.1942C> T (p.Pro648Ser) single nucleotide variant not provided rs768964431 GRCh38 Chromosome 10, 95611424: 95611424
31 ALDH18A1 NM_002860.3(ALDH18A1): c.1568C> T (p.Ala523Val) single nucleotide variant Uncertain significance rs529294368 GRCh37 Chromosome 10, 97376271: 97376271
32 ALDH18A1 NM_002860.3(ALDH18A1): c.1568C> T (p.Ala523Val) single nucleotide variant Uncertain significance rs529294368 GRCh38 Chromosome 10, 95616514: 95616514
33 ALDH18A1 NM_002860.3(ALDH18A1): c.551C> T (p.Ala184Val) single nucleotide variant Uncertain significance rs201428777 GRCh37 Chromosome 10, 97396857: 97396857
34 ALDH18A1 NM_002860.3(ALDH18A1): c.551C> T (p.Ala184Val) single nucleotide variant Uncertain significance rs201428777 GRCh38 Chromosome 10, 95637100: 95637100
35 ALDH18A1 NM_002860.3(ALDH18A1): c.1777A> G (p.Ser593Gly) single nucleotide variant Uncertain significance GRCh37 Chromosome 10, 97373747: 97373747
36 ALDH18A1 NM_002860.3(ALDH18A1): c.1777A> G (p.Ser593Gly) single nucleotide variant Uncertain significance GRCh38 Chromosome 10, 95613990: 95613990
37 ALDH18A1 NM_002860.3(ALDH18A1): c.868G> A (p.Gly290Arg) single nucleotide variant Uncertain significance rs368147360 GRCh37 Chromosome 10, 97388190: 97388190
38 ALDH18A1 NM_002860.3(ALDH18A1): c.868G> A (p.Gly290Arg) single nucleotide variant Uncertain significance rs368147360 GRCh38 Chromosome 10, 95628433: 95628433
39 ALDH18A1 NM_002860.3(ALDH18A1): c.1264C> G (p.Leu422Val) single nucleotide variant Uncertain significance rs142712849 GRCh38 Chromosome 10, 95621234: 95621234
40 ALDH18A1 NM_002860.3(ALDH18A1): c.1264C> G (p.Leu422Val) single nucleotide variant Uncertain significance rs142712849 GRCh37 Chromosome 10, 97380991: 97380991
41 ALDH18A1 NM_002860.3(ALDH18A1): c.1015G> A (p.Val339Ile) single nucleotide variant Uncertain significance GRCh37 Chromosome 10, 97387262: 97387262
42 ALDH18A1 NM_002860.3(ALDH18A1): c.1015G> A (p.Val339Ile) single nucleotide variant Uncertain significance GRCh38 Chromosome 10, 95627505: 95627505
43 ALDH18A1 NM_002860.3(ALDH18A1): c.678C> T (p.Val226=) single nucleotide variant Likely benign rs772829720 GRCh37 Chromosome 10, 97393287: 97393287
44 ALDH18A1 NM_002860.3(ALDH18A1): c.678C> T (p.Val226=) single nucleotide variant Likely benign rs772829720 GRCh38 Chromosome 10, 95633530: 95633530
45 ALDH18A1 NM_002860.3(ALDH18A1): c.1604T> A (p.Leu535Gln) single nucleotide variant Uncertain significance rs200452017 GRCh37 Chromosome 10, 97376235: 97376235
46 ALDH18A1 NM_002860.3(ALDH18A1): c.1604T> A (p.Leu535Gln) single nucleotide variant Uncertain significance rs200452017 GRCh38 Chromosome 10, 95616478: 95616478
47 ALDH18A1 NM_002860.3(ALDH18A1): c.428C> T (p.Ser143Leu) single nucleotide variant Uncertain significance GRCh37 Chromosome 10, 97397069: 97397069
48 ALDH18A1 NM_002860.3(ALDH18A1): c.428C> T (p.Ser143Leu) single nucleotide variant Uncertain significance GRCh38 Chromosome 10, 95637312: 95637312
49 ALDH18A1 NM_002860.3(ALDH18A1): c.1393G> C (p.Glu465Gln) single nucleotide variant Uncertain significance rs757876226 GRCh37 Chromosome 10, 97380862: 97380862
50 ALDH18A1 NM_002860.3(ALDH18A1): c.1393G> C (p.Glu465Gln) single nucleotide variant Uncertain significance rs757876226 GRCh38 Chromosome 10, 95621105: 95621105

Expression for Cutis Laxa, Autosomal Dominant 3

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Pathways for Cutis Laxa, Autosomal Dominant 3

GO Terms for Cutis Laxa, Autosomal Dominant 3

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