MCID: CLD014
MIFTS: 32

Cole Disease

Categories: Genetic diseases, Rare diseases, Skin diseases, Gastrointestinal diseases

Aliases & Classifications for Cole Disease

MalaCards integrated aliases for Cole Disease:

Name: Cole Disease 57 53 25 59 75 37 29 6 40 73
Guttate Hypopigmentation and Punctate Palmoplantar Keratoderma with or Without Ectopic Calcification 57 25
Coled 57 75
Punctate Palmoplantar Keratoderma with or Without Ectopic Calcification 53
Guttate Hypopigmentation and Punctate Palmoplantar Keratoderma 59
Hypopigmentation and Punctate Keratosis of the Palms and Soles 59
Hypopigmentation-Punctate Palmoplantar Keratoderma Syndrome 59
Albinoidism, Oculocutaneous, Autosomal Dominant 73
Hypopigmentation Disorder 73
Guttate Hypopigmentation 53
Hypopigmentation 44
Col 76

Characteristics:

Orphanet epidemiological data:

59
hypopigmentation-punctate palmoplantar keratoderma syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
skin lesions manifest in the first year of life
hair, teeth, and nails are normal


HPO:

32
cole disease:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare skin diseases


External Ids:

OMIM 57 615522
Orphanet 59 ORPHA324561
ICD10 via Orphanet 34 Q82.8
KEGG 37 H01394

Summaries for Cole Disease

OMIM : 57 Cole disease is a rare autosomal dominant disorder characterized by congenital or early-onset punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show nonspecific changes including hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer (summary by Eytan et al., 2013). Some patients also exhibit calcinosis cutis or early-onset calcific tendinopathy (Eytan et al., 2013). (615522)

MalaCards based summary : Cole Disease, also known as guttate hypopigmentation and punctate palmoplantar keratoderma with or without ectopic calcification, is related to yemenite deaf-blind hypopigmentation syndrome and oculocerebral syndrome with hypopigmentation, and has symptoms including achromia of skin An important gene associated with Cole Disease is ENPP1 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 1), and among its related pathways/superpathways are Purine metabolism and Starch and sucrose metabolism. Affiliated tissues include skin, and related phenotypes are hyperkeratosis and epidermal acanthosis

Genetics Home Reference : 25 Cole disease is a disorder that affects the skin. People with this disorder have areas of unusually light-colored skin (hypopigmentation), typically on the arms and legs, and spots of thickened skin on the palms of the hands and the soles of the feet (punctate palmoplantar keratoderma). These skin features are present at birth or develop in the first year of life.

UniProtKB/Swiss-Prot : 75 Cole disease: A rare autosomal dominant genodermatosis characterized by punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer. Some patients also exhibit calcinosis cutis or calcific tendinopathy.

Related Diseases for Cole Disease

Diseases related to Cole Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 72)
# Related Disease Score Top Affiliating Genes
1 yemenite deaf-blind hypopigmentation syndrome 12.4
2 oculocerebral syndrome with hypopigmentation 12.4
3 hyperpigmentation with or without hypopigmentation, familial progressive 12.3
4 cole-carpenter syndrome 1 12.3
5 cole-carpenter syndrome 2 12.3
6 cole-carpenter syndrome 12.2
7 osteoporosis and oculocutaneous hypopigmentation syndrome 12.2
8 oculocerebral hypopigmentation syndrome of preus 12.1
9 raindrop hypopigmentation 12.0
10 tietz albinism-deafness syndrome 11.9
11 dyskeratosis congenita 11.9
12 vici syndrome 11.9
13 hypopigmentation of eyelid 11.8
14 griscelli syndrome 11.8
15 waardenburg syndrome, type 2e 11.6
16 griscelli syndrome, type 2 11.5
17 griscelli syndrome, type 1 11.5
18 dyskeratosis congenita, x-linked 11.2
19 chediak-higashi syndrome 11.1
20 acrocephalopolydactylous dysplasia 11.1
21 macrocephaly, benign familial 11.0
22 dilution, pigmentary 11.0
23 hypomelanotic disorder 11.0
24 obsessive-compulsive disorder 11.0
25 cryohydrocytosis 10.9
26 albinism, ocular, type i 10.9
27 aland island eye disease 10.9
28 reticulate acropigmentation of kitamura 10.9
29 epidermolysis bullosa simplex with mottled pigmentation 10.8
30 waardenburg syndrome, type 3 10.8
31 macular dystrophy, concentric annular 10.8
32 gillespie syndrome 10.8
33 revesz syndrome 10.8
34 rothmund-thomson syndrome 10.8
35 mismatch repair cancer syndrome 10.8
36 hypomelanosis of ito 10.8
37 albinism-deafness syndrome 10.8
38 menkes disease 10.8
39 poikiloderma with neutropenia 10.8
40 albinism, oculocutaneous, type ib 10.8
41 griscelli syndrome, type 3 10.8
42 hyperpigmentation, familial progressive, 1 10.8
43 epidermolysis bullosa simplex, generalized, with scarring and hair loss 10.8
44 ocular albinism, x-linked 10.8
45 carpenter syndrome 1 10.1
46 pneumonia 10.0
47 hermansky-pudlak syndrome 10.0
48 melanoma 10.0
49 stickler syndrome 9.9
50 squamous cell carcinoma 9.9

Graphical network of the top 20 diseases related to Cole Disease:



Diseases related to Cole Disease

Symptoms & Phenotypes for Cole Disease

Symptoms via clinical synopsis from OMIM:

57
Skin Nails Hair Skin Histology:
hyperkeratosis
acanthosis
hypergranulosis
normal number of melanocytes
hyperorthokeratosis
more
Skin Nails Hair Nails:
normal nails

Chest Breasts:
microcalcifications on mammography (in some patients)

Skeletal Pelvis:
calcific tendinopathy of hips (in some patients)

Skeletal Feet:
calcific tendinopathy of heels (in some patients)

Skin Nails Hair Skin Electron Microscopy:
increased melanosomes in cytoplasm and dendrites of melanocytes
paucity of melanosomes in keratinocytes

Skin Nails Hair Hair:
normal hair

Head And Neck Mouth:
normal teeth

AbdomenSpleen:
splenic calcification (in some patients)

Skeletal Limbs:
calcific tendinopathy of shoulders (in some patients)
calcific tendinopathy of wrists (in some patients)

Skin Nails Hair Skin:
hypopigmented macules, primarily on extremities
punctate palmoplantar keratoderma

Muscle Soft Tissue:
calcific tendinopathy, early-onset (in some patients)


Clinical features from OMIM:

615522

Human phenotypes related to Cole Disease:

32
# Description HPO Frequency HPO Source Accession
1 hyperkeratosis 32 HP:0000962
2 epidermal acanthosis 32 HP:0025092
3 hypergranulosis 32 HP:0025114

UMLS symptoms related to Cole Disease:


achromia of skin

Drugs & Therapeutics for Cole Disease

Search Clinical Trials , NIH Clinical Center for Cole Disease

Inferred drug relations via UMLS 73 / NDF-RT 51 :


Cochrane evidence based reviews: hypopigmentation

Genetic Tests for Cole Disease

Genetic tests related to Cole Disease:

# Genetic test Affiliating Genes
1 Cole Disease 29 ENPP1

Anatomical Context for Cole Disease

MalaCards organs/tissues related to Cole Disease:

41
Skin

Publications for Cole Disease

Articles related to Cole Disease:

# Title Authors Year
1
ENPP1 Mutation Causes Recessive Cole Disease by Altering Melanogenesis. ( 28964717 )
2018
2
Association of Cole disease with novel heterozygous mutations in the somatomedin-B domains of the ENPP1 gene: necessary, but not always sufficient. ( 26617416 )
2016
3
Cole disease: a case report and literature review. ( 25065726 )
2014
4
Cole Disease Results from Mutations in ENPP1. ( 24075184 )
2013
5
Palmoplantar hyperkeratoses and hypopigmentation. Cole disease. ( 21597676 )
2011
6
Cole disease: guttate hypopigmentation and punctate palmoplantar keratoderma. ( 19380683 )
2009
7
Cole disease: hypopigmentation with punctate keratosis of the palms and soles. ( 12220272 )
2002

Variations for Cole Disease

UniProtKB/Swiss-Prot genetic disease variations for Cole Disease:

75
# Symbol AA change Variation ID SNP ID
1 ENPP1 p.Cys149Ser VAR_070782 rs397518477
2 ENPP1 p.Cys164Ser VAR_070783 rs397518476
3 ENPP1 p.Cys177Tyr VAR_070784 rs397518475
4 ENPP1 p.Cys133Arg VAR_077257
5 ENPP1 p.Cys177Ser VAR_077258

ClinVar genetic disease variations for Cole Disease:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 ENPP1 NM_006208.2(ENPP1): c.530G> A (p.Cys177Tyr) single nucleotide variant Pathogenic rs397518475 GRCh37 Chromosome 6, 132172381: 132172381
2 ENPP1 NM_006208.2(ENPP1): c.530G> A (p.Cys177Tyr) single nucleotide variant Pathogenic rs397518475 GRCh38 Chromosome 6, 131851241: 131851241
3 ENPP1 NM_006208.2(ENPP1): c.491G> C (p.Cys164Ser) single nucleotide variant Pathogenic rs397518476 GRCh37 Chromosome 6, 132172342: 132172342
4 ENPP1 NM_006208.2(ENPP1): c.491G> C (p.Cys164Ser) single nucleotide variant Pathogenic rs397518476 GRCh38 Chromosome 6, 131851202: 131851202
5 ENPP1 NM_006208.2(ENPP1): c.446G> C (p.Cys149Ser) single nucleotide variant Pathogenic rs397518477 GRCh37 Chromosome 6, 132172297: 132172297
6 ENPP1 NM_006208.2(ENPP1): c.446G> C (p.Cys149Ser) single nucleotide variant Pathogenic rs397518477 GRCh38 Chromosome 6, 131851157: 131851157
7 ENPP1 NM_006208.2(ENPP1): c.288delG (p.Leu97Terfs) deletion Pathogenic GRCh37 Chromosome 6, 132168963: 132168963
8 ENPP1 NM_006208.2(ENPP1): c.288delG (p.Leu97Terfs) deletion Pathogenic GRCh38 Chromosome 6, 131847823: 131847823

Expression for Cole Disease

Search GEO for disease gene expression data for Cole Disease.

Pathways for Cole Disease

Pathways related to Cole Disease according to KEGG:

37
# Name Kegg Source Accession
1 Purine metabolism hsa00230
2 Starch and sucrose metabolism hsa00500
3 Riboflavin metabolism hsa00740
4 Nicotinate and nicotinamide metabolism hsa00760
5 Pantothenate and CoA biosynthesis hsa00770

GO Terms for Cole Disease

Sources for Cole Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....