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 53 49 24 55 71 36 28 69
Guttate Hypopigmentation and Punctate Palmoplantar Keratoderma with or Without Ectopic Calcification 53 24
Coled 53 71
Punctate Palmoplantar Keratoderma with or Without Ectopic Calcification 49
Guttate Hypopigmentation and Punctate Palmoplantar Keratoderma 55
Hypopigmentation and Punctate Keratosis of the Palms and Soles 55
Hypopigmentation-Punctate Palmoplantar Keratoderma Syndrome 55
Albinoidism, Oculocutaneous, Autosomal Dominant 69
Hypopigmentation Disorder 69
Guttate Hypopigmentation 49
Hypopigmentation 41
Col 72

Characteristics:

Orphanet epidemiological data:

55
hypopigmentation-punctate palmoplantar keratoderma syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal dominant

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


HPO:

31
cole disease:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 55  
Rare skin diseases


External Ids:

OMIM 53 615522
Orphanet 55 ORPHA324561
ICD10 via Orphanet 33 Q82.8
KEGG 36 H01394

Summaries for Cole Disease

OMIM : 53 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 hyperkeratosis, epidermal acanthosis and hypergranulosis. 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.

Genetics Home Reference : 24 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 : 71 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

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:

53
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

Abdomen Spleen:
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:

31
# Description HPO Frequency HPO Source Accession
1 hyperkeratosis 31 HP:0000962
2 epidermal acanthosis 31 HP:0025092
3 hypergranulosis 31 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 69 / NDF-RT 47 :


Cochrane evidence based reviews: hypopigmentation

Genetic Tests for Cole Disease

Genetic tests related to Cole Disease:

# Genetic test Affiliating Genes
1 Cole Disease 28 ENPP1

Anatomical Context for Cole Disease

MalaCards organs/tissues related to Cole Disease:

38
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:

71
# 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.491G> C (p.Cys164Ser) single nucleotide variant Pathogenic rs397518476 GRCh37 Chromosome 6, 132172342: 132172342
3 ENPP1 NM_006208.2(ENPP1): c.446G> C (p.Cys149Ser) single nucleotide variant Pathogenic rs397518477 GRCh37 Chromosome 6, 132172297: 132172297

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:

36
# 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
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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