MDM
MCID: MLD006
MIFTS: 44

Mal De Meleda (MDM)

Categories: Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Mal De Meleda

MalaCards integrated aliases for Mal De Meleda:

Name: Mal De Meleda 56 12 52 25 58 73 36 54 15
Meleda Disease 56 12 74 52 25 58 73 13 71
Keratosis Palmoplantaris Transgrediens of Siemens 56 12 25 58
Acroerythrokeratoderma 25 29 6 39
Transgrediens Palmoplantar Keratoderma of Siemens 12 25 58
Mdm 56 52 73
Keratosis Palmoplantaris Transgradiens of Siemens 52 73

Characteristics:

Orphanet epidemiological data:

58
mal de meleda
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset in early infancy


HPO:

31
mal de meleda:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare skin diseases


External Ids:

Disease Ontology 12 DOID:0060862
OMIM 56 248300
KEGG 36 H00695
MeSH 43 D007645
ICD10 32 Q82.8
ICD10 via Orphanet 33 Q82.8
UMLS via Orphanet 72 C0025221
Orphanet 58 ORPHA87503
MedGen 41 C0025221
UMLS 71 C0025221

Summaries for Mal De Meleda

Genetics Home Reference : 25 Mal de Meleda is a rare skin disorder that begins in early infancy. Affected individuals have a condition known as palmoplantar keratoderma, in which the skin of the palms of the hands and soles of the feet becomes thick, hard, and callused. In mal de Meleda, the thickened skin is also found on the back of the hands and feet and on the wrists and ankles. In addition, affected individuals may have rough, thick pads on the joints of the fingers and toes and on the elbows and knees. Some people with mal de Meleda have recurrent fungal infections in the thickened skin, which can lead to a strong odor. Other features of this disorder can include short fingers and toes (brachydactyly), nail abnormalities, red skin around the mouth, and excessive sweating (hyperhidrosis).

MalaCards based summary : Mal De Meleda, also known as meleda disease, is related to palmoplantar keratosis and palmoplantar keratoderma, nagashima type. An important gene associated with Mal De Meleda is SLURP1 (Secreted LY6/PLAUR Domain Containing 1), and among its related pathways/superpathways is Post-translational modification- synthesis of GPI-anchored proteins. Affiliated tissues include skin and t cells, and related phenotypes are diffuse palmoplantar keratoderma and hyperkeratosis with erythema

Disease Ontology : 12 A palmoplantar keratosis characterized by autosomal recessive inheritance of symmetric palmoplantar hyperkeratosis that progressively extends to the dorsal surfaces of hands and feet and ichthyotic changes elsewhere that has material basis in homozygous mutation in the SLURP1 gene on chromosome 8q24.

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 87503 Definition Mal de Meleda (MdM) is a diffuse palmoplantar keratoderma, initially reported in the Island of Meleda, characterized by symmetric palmoplantar hyperkeratosis that progressively extends to the dorsal surfaces of hands and feet (transgrediens). The disease can be associated to hyperhidrosis, lichenoid plaques and perioral erythema. Visit the Orphanet disease page for more resources.

KEGG : 36 Mal de Meleda is an autosomal recessive palmoplantar keratoderma characterized by erythema of the palms and soles, followed by a diffuse yellowish hyperkeratosis. Keratinization extends onto the dorsal surface of the hands and feet as the patient ages. It is associated with brachydactyly and nail abnormalities. Mental retardation may also occur.

UniProtKB/Swiss-Prot : 73 Mal de Meleda: A rare autosomal recessive skin disorder, characterized by diffuse transgressive palmoplantar keratoderma with keratotic lesions extending onto the dorsa of the hands and the feet (transgrediens). Patients may have hyperhidrosis. Other features include perioral erythema, lichenoid plaques on the knees and the elbows, and nail abnormalities.

Wikipedia : 74 Meleda disease (MDM) or "mal de Meleda", also called Mljet disease, keratosis palmoplantaris and... more...

More information from OMIM: 248300

Related Diseases for Mal De Meleda

Diseases related to Mal De Meleda via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 56)
# Related Disease Score Top Affiliating Genes
1 palmoplantar keratosis 30.6 SLURP1 SERPINB7 PLAUR LYNX1
2 palmoplantar keratoderma, nagashima type 11.7
3 papillon-lefevre syndrome 11.6
4 keratosis 10.9
5 skin disease 10.6
6 brachydactyly 10.6
7 pseudoainhum 10.6
8 erythrokeratoderma ''en cocardes'' 10.5
9 keratoderma palmoplantaris transgrediens 10.5
10 hereditary palmoplantar keratoderma 10.5
11 myositis 10.4
12 muscular dystrophy 10.4
13 ainhum 10.4
14 knuckle pads 10.4
15 cataract 10.4
16 diffuse palmoplantar keratoderma 10.4
17 erythrokeratoderma 10.4
18 leprosy 3 10.2
19 naxos disease 10.2
20 melanoma, cutaneous malignant 10 10.2
21 autosomal recessive disease 10.2
22 dermatomycosis 10.2
23 squamous cell carcinoma 10.2
24 cheilitis 10.2
25 melanoma 10.2
26 amelanotic melanoma 10.2
27 bowen's disease 10.2
28 hansen's disease 10.2
29 rare genetic skin disease 10.2
30 tibial muscular dystrophy 10.2
31 limb-girdle muscular dystrophy 10.2
32 ovarian cancer 10.0
33 papillomatosis, confluent and reticulated 10.0
34 retinoblastoma 10.0
35 suppressor of tumorigenicity 3 10.0
36 muscular dystrophy, limb-girdle, autosomal recessive 1 10.0
37 cervical cancer 10.0
38 oral squamous cell carcinoma 10.0
39 pain agnosia 10.0
40 beta-lactam allergy 10.0
41 bone sarcoma 10.0
42 glioblastoma multiforme 10.0
43 rhabdomyosarcoma 10.0
44 familial retinoblastoma 10.0
45 glioma 10.0
46 lymphosarcoma 10.0
47 glial tumor 10.0
48 progressive muscular dystrophy 10.0
49 posttransplant acute limbic encephalitis 10.0
50 early-onset lamellar cataract 9.9 HSF4 CRYAA

Graphical network of the top 20 diseases related to Mal De Meleda:



Diseases related to Mal De Meleda

Symptoms & Phenotypes for Mal De Meleda

Human phenotypes related to Mal De Meleda:

58 31 (show all 13)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 diffuse palmoplantar keratoderma 58 31 hallmark (90%) Very frequent (99-80%) HP:0007435
2 hyperkeratosis with erythema 58 31 hallmark (90%) Very frequent (99-80%) HP:0007390
3 ichthyosis 58 31 frequent (33%) Frequent (79-30%) HP:0008064
4 hyperhidrosis 58 31 frequent (33%) Frequent (79-30%) HP:0000975
5 concave nail 58 31 frequent (33%) Frequent (79-30%) HP:0001598
6 subungual hyperkeratosis 58 31 frequent (33%) Frequent (79-30%) HP:0008392
7 onychogryposis 31 frequent (33%) HP:0001805
8 erythema 31 HP:0010783
9 brachydactyly 31 HP:0001156
10 abnormality of the mouth 31 HP:0000153
11 thick nail 58 Frequent (79-30%)
12 fragile nails 31 HP:0001808
13 congenital symmetrical palmoplantar keratosis 31 HP:0007553

Symptoms via clinical synopsis from OMIM:

56
Skin Nails Hair Skin:
ichthyosis
hyperhidrosis
congenital symmetrical palmoplantar keratosis
transgressive keratosis
lichenoid plaques

Head And Neck Mouth:
perioral erythema

Skeletal Hands:
brachydactyly

Skin Nails Hair Nails:
fragile, lustreless nails

Clinical features from OMIM:

248300

Drugs & Therapeutics for Mal De Meleda

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Role of SLURP-1 in Melanoma and Melanoma Stem Cells Unknown status NCT01281722

Search NIH Clinical Center for Mal De Meleda

Genetic Tests for Mal De Meleda

Genetic tests related to Mal De Meleda:

# Genetic test Affiliating Genes
1 Acroerythrokeratoderma 29 SLURP1

Anatomical Context for Mal De Meleda

MalaCards organs/tissues related to Mal De Meleda:

40
Skin, T Cells

Publications for Mal De Meleda

Articles related to Mal De Meleda:

(show top 50) (show all 143)
# Title Authors PMID Year
1
Mutations in the gene encoding SLURP-1 in Mal de Meleda. 54 56 6 61
11285253 2001
2
Heterozygous manifestations in female carriers of Mal de Meleda. 56 6 61
14756676 2004
3
A novel missense mutation in the gene encoding SLURP-1 in patients with Mal de Meleda from northern Tunisia. 56 6 61
14674887 2003
4
Genetic linkage of Meleda disease to chromosome 8qter. 56 61 6
9887370 1998
5
Further evidence of the clinical and genetic heterogeneity of recessive transgressive PPK in the Mediterranean region. 54 61 56
16865292 2006
6
Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda. 56 61 54
14506129 2003
7
Mal de Meleda without mutations in the ARS coding sequence. 56 61 54
11872406 2002
8
Mal de Meleda (MDM) caused by mutations in the gene for SLURP-1 in patients from Germany, Turkey, Palestine, and the United Arab Emirates. 61 6
12483299 2003
9
[Meleda disease]. 61 56
4281438 1972
10
[Autochthonous Meleda disease]. 56 61
5367495 1969
11
Genetic and clinical heterogeneity in transgressive palmoplantar keratoderma. 56
11348480 2001
12
[Contribution to the problem of Mljet's disease (Meleda's disease)]. 56
14496272 1961
13
Mutations in the SLURP-1 gene underlie Mal de Meleda in three Pakistani families. 54 61
19692209 2009
14
Expression of SLURP-1, an endogenous alpha7 nicotinic acetylcholine receptor allosteric ligand, in murine bronchial epithelial cells. 54 61
19396877 2009
15
"Nagashima-type" keratosis as a novel entity in the palmoplantar keratoderma category. 61 54
18347294 2008
16
SLURP1 is a late marker of epidermal differentiation and is absent in Mal de Meleda. 54 61
17008884 2007
17
A novel mutation in the ARS (component B) gene encoding SLURP-1 in a Turkish family with mal de Meleda. 61 54
16882192 2006
18
Mendelian diseases and conditions in Croatian island populations: historic records and new insights. 54 61
16909451 2006
19
Mal de Meleda in a taiwanese. 54 61
15909066 2005
20
ARS Component B: structural characterization, tissue expression and regulation of the gene and protein (SLURP-1) associated with Mal de Meleda. 61 54
14721776 2003
21
A novel mutation in the ARS (component B) gene encoding SLURP-1 in a family with Mal de Meleda. 61 54
12950349 2003
22
A recurrent mutation in the ARS (component B) gene encoding SLURP-1 in Turkish families with mal de Meleda: evidence of a founder effect. 54 61
12787122 2003
23
Novel mutations in the gene encoding secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related protein-1 (SLURP-1) and description of five ancestral haplotypes in patients with Mal de Meleda. 61 54
12603845 2003
24
Identification of recurrent mutations in the ARS (component B) gene encoding SLURP-1 in two families with mal de Meleda. 61 54
12535203 2003
25
Mal de Meleda with homozygous mutation p.G86R in SLURP-1. 61
32048728 2020
26
Abnormal keratinization and cutaneous inflammation in Mal de Meleda. 61
32157724 2020
27
Identification of a CDH12 potential candidate genetic variant for an autosomal dominant form of transgrediens and progrediens palmoplantar keratoderma in a Tunisian family. 61
31911611 2020
28
In-silico Analyses of Disease Causing Mutations in SLURP1 Gene. 61
31882421 2019
29
[Acral melanoma in a patient with hereditary keratoderma of the palms and soles (mal de Meleda): A chance association?] 61
31582262 2019
30
Novel nonsense variants in SLURP1 and DSG1 cause palmoplantar keratoderma in Pakistani families. 61
31443639 2019
31
Amelanotic melanoma arising in an area of SLURP-1 mutated Mal de Meleda. 61
30246339 2019
32
Japanese case of Mal de Meleda with a novel missense mutation of p.Thr52Ala in the second protruding finger of secreted Ly-6/uPAR-related protein 1. 61
30663803 2019
33
Patient with Mal de Meleda in whom a Novel Gene Mutation was Identified. 61
31258365 2019
34
Mal de Meleda: A great imitator. 61
31178100 2019
35
SLURP-1 is mutated in Mal de Meleda, a potential molecular signature for melanoma and a putative squamous lineage tumor suppressor gene. 61
29231248 2018
36
A hypomorphic Egfr allele does not ameliorate the palmoplantar keratoderma caused by SLURP1 deficiency. 61
28418591 2017
37
Identification of novel homozygous SLURP1 mutation in a Javanese family with Mal de Meleda. 61
29023701 2017
38
A Mal De Meleda patient with severe flexion contractures of hands and feet: A case report in West China. 61
28885351 2017
39
Nagashima-type palmoplantar keratosis in a Chinese Han population. 61
27666198 2016
40
A novel homozygous mutation disrupting the initiation codon in the SLURP1 gene underlies mal de Meleda in a consanguineous family. 61
29226984 2016
41
Immunohistological study of tight junction protein expression in mal de Meleda. 61
26986447 2016
42
Malignant melanoma in a patient with mal de Meleda. 61
26801819 2016
43
A Different Presentation of Mal De Meleda: New Skin Lesions in a Residual Limb after Traumatic Amputation. 61
27477174 2016
44
First Mal de Meleda report in Chinese Mainland: two families with a recurrent homozygous missense mutation in SLURP-1. 61
25763536 2016
45
Unguales Plattenepithelkarzinom bei einem Patienten mit Mal de Meleda. 61
27119476 2016
46
Ungual squamous cell carcinoma in a patient with Mal de Meleda. 61
27119475 2016
47
Cutaneous mosaicism, in KRT1 pI479T patient, caused by the somatic loss of the wild-type allele, leads to the increase in local severity of the disease. 61
25904304 2016
48
Mal de Meleda in Indonesia: Mutations in the SLURP1 gene appear to be ubiquitous. 61
25557416 2016
49
Mal de Meleda: A Focused Review. 61
26445964 2016
50
Palmoplantar Keratoderma in Slurp2-Deficient Mice. 61
26967477 2016

Variations for Mal De Meleda

ClinVar genetic disease variations for Mal De Meleda:

6 (show all 24) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SLURP1 NM_020427.3(SLURP1):c.82del (p.Cys28fs)deletion Pathogenic 4599 rs587776601 8:143823317-143823317 8:142741899-142741899
2 SLURP1 NM_020427.3(SLURP1):c.178+1G>ASNV Pathogenic 4600 rs587776602 8:143823220-143823220 8:142741802-142741802
3 SLURP1 NM_020427.3(SLURP1):c.286C>T (p.Arg96Ter)SNV Pathogenic 4601 rs121908317 8:143822587-143822587 8:142741169-142741169
4 SLURP1 NM_020427.3(SLURP1):c.256G>A (p.Gly86Arg)SNV Pathogenic 4602 rs28937888 8:143822617-143822617 8:142741199-142741199
5 SLURP1 NM_020427.3(SLURP1):c.256G>C (p.Gly86Arg)SNV Pathogenic 4603 rs28937888 8:143822617-143822617 8:142741199-142741199
6 SLURP1 NM_020427.3(SLURP1):c.1A>C (p.Met1Leu)SNV Pathogenic 4604 rs28937889 8:143823803-143823803 8:142742385-142742385
7 SLURP1 NM_020427.3(SLURP1):c.43T>C (p.Trp15Arg)SNV Pathogenic 4605 rs121908318 8:143823761-143823761 8:142742343-142742343
8 SLURP1 NM_020427.3(SLURP1):c.229T>C (p.Cys77Arg)SNV Pathogenic 4606 rs121908319 8:143822644-143822644 8:142741226-142741226
9 SLURP1 NM_020427.3(SLURP1):c.296G>A (p.Cys99Tyr)SNV Pathogenic 4607 rs121908320 8:143822577-143822577 8:142741159-142741159
10 SLURP1 NM_020427.3(SLURP1):c.310T>C (p.Ter104Arg)SNV Conflicting interpretations of pathogenicity 502120 rs62636565 8:143822563-143822563 8:142741145-142741145
11 SLURP1 NM_020427.3(SLURP1):c.*146G>ASNV Uncertain significance 910652 8:143822415-143822415 8:142740997-142740997
12 SLURP1 NM_020427.3(SLURP1):c.*10G>ASNV Uncertain significance 911881 8:143822551-143822551 8:142741133-142741133
13 SLURP1 NM_020427.3(SLURP1):c.202G>A (p.Val68Met)SNV Uncertain significance 911882 8:143822671-143822671 8:142741253-142741253
14 SLURP1 NM_020427.3(SLURP1):c.167C>T (p.Thr56Met)SNV Uncertain significance 911883 8:143823232-143823232 8:142741814-142741814
15 SLURP1 NM_020427.3(SLURP1):c.158C>T (p.Thr53Met)SNV Uncertain significance 908937 8:143823241-143823241 8:142741823-142741823
16 SLURP1 NM_020427.3(SLURP1):c.141C>T (p.Asp47=)SNV Uncertain significance 908938 8:143823258-143823258 8:142741840-142741840
17 SLURP1 NM_020427.3(SLURP1):c.125G>A (p.Arg42His)SNV Uncertain significance 908939 8:143823274-143823274 8:142741856-142741856
18 SLURP1 NM_020427.3(SLURP1):c.47G>T (p.Ser16Ile)SNV Uncertain significance 908940 8:143823757-143823757 8:142742339-142742339
19 SLURP1 NM_020427.3(SLURP1):c.10C>T (p.Arg4Cys)SNV Uncertain significance 77205 rs267601807 8:143823794-143823794 8:142742376-142742376
20 SLURP1 NM_020427.3(SLURP1):c.179-3C>TSNV Uncertain significance 362101 rs371317832 8:143822697-143822697 8:142741279-142741279
21 SLURP1 NM_020427.3(SLURP1):c.-7C>TSNV Uncertain significance 362102 rs201610070 8:143823810-143823810 8:142742392-142742392
22 SLURP1 NM_020427.3(SLURP1):c.*14G>ASNV Uncertain significance 362099 rs886062732 8:143822547-143822547 8:142741129-142741129
23 SLURP1 NM_020427.3(SLURP1):c.*143G>ASNV Likely benign 362098 rs182887603 8:143822418-143822418 8:142741000-142741000
24 SLURP1 NM_020427.3(SLURP1):c.261C>T (p.Ala87=)SNV Benign 362100 rs62636564 8:143822612-143822612 8:142741194-142741194

UniProtKB/Swiss-Prot genetic disease variations for Mal De Meleda:

73
# Symbol AA change Variation ID SNP ID
1 SLURP1 p.Trp15Arg VAR_032871 rs121908318
2 SLURP1 p.Arg71His VAR_032872 rs144801716
3 SLURP1 p.Cys77Arg VAR_032873 rs121908319
4 SLURP1 p.Gly86Arg VAR_032874 rs28937888
5 SLURP1 p.Cys99Tyr VAR_032875 rs121908320
6 SLURP1 p.Arg71Pro VAR_077307
7 SLURP1 p.Cys94Ser VAR_077309 rs772388665
8 SLURP1 p.Leu98Pro VAR_077310

Expression for Mal De Meleda

Search GEO for disease gene expression data for Mal De Meleda.

Pathways for Mal De Meleda

Pathways related to Mal De Meleda according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.02 PLAUR LYPD5 LYPD3 LYPD2 GPIHBP1

GO Terms for Mal De Meleda

Cellular components related to Mal De Meleda according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.56 SLURP1 PLAUR PATE3 LYPD5 LYPD3 LYPD2
2 anchored component of membrane GO:0031225 9.17 PLAUR LYPD5 LYPD3 LYPD2 LYNX1 LY6L

Biological processes related to Mal De Meleda according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of signaling receptor activity GO:2000272 9.26 LYNX1 GPIHBP1
2 positive regulation of DNA binding GO:0043388 9.16 PLAUR EGF
3 regulation of neurotransmitter receptor activity GO:0099601 8.96 SLURP1 LYNX1
4 urokinase plasminogen activator signaling pathway GO:0038195 8.62 SLURP1 PLAUR

Molecular functions related to Mal De Meleda according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 laminin binding GO:0043236 8.96 LYPD5 LYPD3
2 acetylcholine receptor inhibitor activity GO:0030550 8.62 LYNX1 GPIHBP1

Sources for Mal De Meleda

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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