PLCA3
MCID: AMY111
MIFTS: 32

Amyloidosis, Primary Localized Cutaneous, 3 (PLCA3)

Categories: Genetic diseases, Metabolic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Amyloidosis, Primary Localized Cutaneous, 3

MalaCards integrated aliases for Amyloidosis, Primary Localized Cutaneous, 3:

Name: Amyloidosis, Primary Localized Cutaneous, 3 56 73 29 6
Amyloidosis Cutis Dyschromica 56 58 73
Amyloidosis Cutis Dyschromia 58 29
Plca3 56 73
Acd 56 73
Amyloidosis Cutis Dyschromica; Acd 56

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset in first decade of life
dyschromia increases and spreads initially then stabilizes
relative sparing of face and neck


HPO:

31
amyloidosis, primary localized cutaneous, 3:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare skin diseases


External Ids:

OMIM 56 617920
OMIM Phenotypic Series 56 PS105250
MeSH 43 D028226
ICD10 via Orphanet 33 E85.4+ L99.0*
Orphanet 58 ORPHA319635

Summaries for Amyloidosis, Primary Localized Cutaneous, 3

UniProtKB/Swiss-Prot : 73 Amyloidosis, primary localized cutaneous, 3: A primary amyloidosis characterized by localized cutaneous amyloid deposition. This condition usually presents with itching (especially on the lower legs) and visible changes of skin hyperpigmentation and thickening that may be exacerbated by chronic scratching and rubbing. Primary localized cutaneous amyloidosis is often divided into macular and lichen subtypes although many affected individuals often show both variants coexisting. Lichen amyloidosis characteristically presents as a pruritic eruption of grouped hyperkeratotic papules with a predilection for the shins, calves, ankles and dorsa of feet and thighs. Papules may coalesce to form hyperkeratotic plaques that can resemble lichen planus, lichen simplex or nodular prurigo. Macular amyloidosis is characterized by small pigmented macules that may merge to produce macular hyperpigmentation, sometimes with a reticulate or rippled pattern. In macular and lichen amyloidosis, amyloid is deposited in the papillary dermis in association with grouped colloid bodies, thought to represent degenerate basal keratinocytes. The amyloid deposits probably reflect a combination of degenerate keratin filaments, serum amyloid P component, and deposition of immunoglobulins. PLCA3 inheritance is autosomal recessive.

MalaCards based summary : Amyloidosis, Primary Localized Cutaneous, 3, also known as amyloidosis cutis dyschromica, is related to alveolar capillary dysplasia with misalignment of pulmonary veins and dyskeratosis congenita, autosomal dominant 6. An important gene associated with Amyloidosis, Primary Localized Cutaneous, 3 is GPNMB (Glycoprotein Nmb). Affiliated tissues include skin and neutrophil, and related phenotypes are dry skin and pruritus

OMIM : 56 Amyloidosis cutis dyschromica (ACD), a rare form of primary localized cutaneous amyloidosis, is a pigmentary disorder in which keratinocyte-derived amyloid is deposited in the skin. Onset occurs before puberty and involves macular or reticulate hyperpigmentation admixed with symmetrically distributed guttate hypopigmented and hyperpigmented lesions. ACD can be distinguished from other conditions with similar clinical findings by a skin biopsy in which amyloid deposition in the papillary dermis is seen. Specific features that set ACD apart from the more common macular and lichenoid variants of primary cutaneous amyloidosis include dotted, reticular, or diffuse hyperpigmentation admixed with lentil-sized hypopigmented macules; mild or no associated pruritus; and, on histologic examination of skin from both hyper- and hypopigmented lesions, amyloid deposition confined to the papillary dermis, in close proximity to the epidermis (Huang et al. (2009); Mahon et al., 2016). For a discussion of genetic heterogeneity of primary localized cutaneous amyloidosis, see 105250. (617920)

Related Diseases for Amyloidosis, Primary Localized Cutaneous, 3

Diseases in the Primary Cutaneous Amyloidosis family:

Amyloidosis, Primary Localized Cutaneous, 1 Amyloidosis, Primary Localized Cutaneous, 2
Amyloidosis, Primary Localized Cutaneous, 3

Diseases related to Amyloidosis, Primary Localized Cutaneous, 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 113)
# Related Disease Score Top Affiliating Genes
1 alveolar capillary dysplasia with misalignment of pulmonary veins 12.4
2 dyskeratosis congenita, autosomal dominant 6 12.2
3 dyskeratosis congenita 12.1
4 alopecia-contractures-dwarfism mental retardation syndrome 12.1
5 hoyeraal hreidarsson syndrome 12.0
6 allergic contact dermatitis 11.8
7 melanoma, cutaneous malignant 1 11.6
8 aplastic anemia 11.6
9 alopecia-contractures-dwarfism-intellectual disability syndrome 11.5
10 corneal dystrophy, avellino type 11.4
11 cone-rod dystrophy 2 11.3
12 osteoporosis 11.3
13 dyskeratosis congenita autosomal dominant 11.3
14 dyskeratosis congenita autosomal recessive 11.3
15 acrofacial dysostosis, catania type 11.2
16 acute cholinergic dysautonomia 11.2
17 campomelic dysplasia 11.2
18 lactase deficiency, congenital 11.1
19 revesz syndrome 11.1
20 febrile seizures, familial, 4 11.1
21 retinitis pigmentosa 50 11.1
22 hereditary lymphedema 11.1
23 hereditary lymphedema i 11.1
24 frontometaphyseal dysplasia 11.1
25 scleromalacia perforans 11.1
26 amyloidosis 11.0
27 primary cutaneous amyloidosis 10.9
28 dowling-degos disease 1 10.8
29 hereditary amyloidosis 10.5
30 telangiectasis 10.4
31 cardiac arrest 10.4
32 contact dermatitis 10.4
33 ventricular fibrillation, paroxysmal familial, 1 10.3
34 dermatitis 10.3
35 autoimmune disease 10.3
36 scleroderma, familial progressive 10.3
37 vitiligo-associated multiple autoimmune disease susceptibility 6 10.3
38 familial mediterranean fever 10.3
39 vitiligo-associated multiple autoimmune disease susceptibility 1 10.3
40 pigmentation disease 10.3
41 brucellosis 10.3
42 palmoplantar keratosis 10.3
43 spasticity 10.3
44 macular amyloidosis 10.3
45 hyperpigmentation of the skin 10.3
46 ductal carcinoma in situ 10.2
47 in situ carcinoma 10.2
48 hydronephrosis 10.2
49 alopecia 10.2
50 breast cancer 10.1

Graphical network of the top 20 diseases related to Amyloidosis, Primary Localized Cutaneous, 3:



Diseases related to Amyloidosis, Primary Localized Cutaneous, 3

Symptoms & Phenotypes for Amyloidosis, Primary Localized Cutaneous, 3

Human phenotypes related to Amyloidosis, Primary Localized Cutaneous, 3:

31
# Description HPO Frequency HPO Source Accession
1 dry skin 31 HP:0000958
2 pruritus 31 HP:0000989
3 hypermelanotic macule 31 HP:0001034

Symptoms via clinical synopsis from OMIM:

56
Skin Nails Hair Skin:
dry skin
hyperpigmented macules
hypopigmented macules
few pruritic papules
pruritis, mild
more
Skin Nails Hair Skin Electron Microscopy:
fibrillar aggregates near epidermal-dermal junction of hyperpigmented lesions
fibrillar aggregates in borders of hypo- and depigmented lesions

Skin Nails Hair Skin Histology:
amorphous eosinophilic material in papillary dermis
increased melanin in basal layer
amyloid deposits enriched in hyperpigmented lesions
elongated ridges surrounding hyperpigmented lesions
infiltration of immune cells around hyperpigmented lesions
more

Clinical features from OMIM:

617920

Drugs & Therapeutics for Amyloidosis, Primary Localized Cutaneous, 3

Search Clinical Trials , NIH Clinical Center for Amyloidosis, Primary Localized Cutaneous, 3

Genetic Tests for Amyloidosis, Primary Localized Cutaneous, 3

Genetic tests related to Amyloidosis, Primary Localized Cutaneous, 3:

# Genetic test Affiliating Genes
1 Amyloidosis, Primary Localized Cutaneous, 3 29 GPNMB
2 Amyloidosis Cutis Dyschromia 29

Anatomical Context for Amyloidosis, Primary Localized Cutaneous, 3

MalaCards organs/tissues related to Amyloidosis, Primary Localized Cutaneous, 3:

40
Skin, Neutrophil

Publications for Amyloidosis, Primary Localized Cutaneous, 3

Articles related to Amyloidosis, Primary Localized Cutaneous, 3:

(show all 27)
# Title Authors PMID Year
1
Loss of GPNMB Causes Autosomal-Recessive Amyloidosis Cutis Dyschromica in Humans. 61 6 56
29336782 2018
2
Amyloidosis cutis dyschromica: four cases from two families. 6 61 56
19416385 2009
3
Amyloidosis cutis dyschromica in two siblings and review of the epidemiology, clinical features and management in 48 cases. 61 56
25866143 2016
4
Molecular basis and inheritance patterns of amyloidosis cutis dyschromica. 61
32097499 2020
5
Three novel mutations in GPNMB in two pedigrees with amyloidosis cutis dyschromica. 61
31260093 2019
6
Semidominant GPNMB Mutations in Amyloidosis Cutis Dyschromica. 61
31226264 2019
7
Case of amyloidosis cutis dyschromica with palmoplantar keratoderma. 61
30912135 2019
8
Amyloidosis cutis dyschromica: report of 3 cases. 61
31329390 2019
9
Primary Localized Cutaneous Amyloidosis Affecting Female Individuals of a Pakistani Pedigree. 61
30308545 2019
10
Late-onset amyloidosis cutis dyschromica: an unusual case. 61
31046910 2019
11
Case of amyloidosis cutis dyschromica with dermoscopy. 61
30126033 2019
12
Amyloidosis Cutis Dyschromica, a Rare Cause of Hyperpigmentation: A New Case and Literature Review. 61
28557715 2017
13
Association of amyloidosis cutis dyschromica and familial Mediterranean fever. 61
29267436 2017
14
Amyloidosis Cutis Dyschromica: A Rare Reticulate Pigmentary Dermatosis. 61
26288409 2015
15
Familial amyloidosis cutis dyschromica in three siblings: report from indonesia. 61
25386328 2014
16
Familial amyloidosis cutis dyschromica: a case report. 61
24659076 2014
17
Amyloidosis cutis dyschromica. 61
24350022 2013
18
Amyloidosis cutis dyschromica. 61
23234252 2012
19
Amyloidosis cutis dyschromica associated with atypical Parkinsonism, spasticity and motor weakness in a Pakistani female. 61
21645034 2011
20
Amyloidosis cutis dyschromica: a rare pigmentary disorder. 61
21592180 2011
21
Amyloidosis cutis dyschromica in two female siblings: cases report. 61
21320354 2011
22
A rare type of primary cutaneous amyloidosis: amyloidosis cutis dyschromica. 61
21091677 2010
23
Amyloidosis cutis dyschromica: a case treated with acitretin. 61
16043923 2005
24
Amyloidosis cutis dyschromica in a patient with generalized morphoea. 61
15030364 2004
25
Familial amyloidosis cutis dyschromica: six cases from three families. 61
12184644 2002
26
Amyloidosis cutis dyschromica in two siblings. 61
11722454 2001
27
Amyloidosis cutis dyschromica. DNA repair reduction in the cellular response to UV light. 61
1626966 1992

Variations for Amyloidosis, Primary Localized Cutaneous, 3

ClinVar genetic disease variations for Amyloidosis, Primary Localized Cutaneous, 3:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GPNMB NM_002510.3(GPNMB):c.565C>T (p.Arg189Ter)SNV Pathogenic 503497 rs140352180 7:23299622-23299622 7:23260003-23260003
2 GPNMB NM_002510.3(GPNMB):c.660T>G (p.Tyr220Ter)SNV Pathogenic 503498 rs770211260 7:23299717-23299717 7:23260098-23260098
3 GPNMB NM_002510.3(GPNMB):c.1056del (p.Pro353fs)deletion Pathogenic 503499 rs763065333 7:23306172-23306172 7:23266553-23266553
4 GPNMB NM_002510.3(GPNMB):c.296del (p.Asn99fs)deletion Pathogenic 503500 rs1554300664 7:23293859-23293859 7:23254240-23254240
5 GPNMB NM_002510.3(GPNMB):c.717_718TG[1] (p.Val240fs)short repeat Pathogenic 503501 rs747723062 7:23300091-23300092 7:23260472-23260473
6 GPNMB NM_002510.3(GPNMB):c.873_876GTTT[1] (p.Val293fs)short repeat Pathogenic 503502 rs773435101 7:23300246-23300249 7:23260627-23260630

Expression for Amyloidosis, Primary Localized Cutaneous, 3

Search GEO for disease gene expression data for Amyloidosis, Primary Localized Cutaneous, 3.

Pathways for Amyloidosis, Primary Localized Cutaneous, 3

GO Terms for Amyloidosis, Primary Localized Cutaneous, 3

Sources for Amyloidosis, Primary Localized Cutaneous, 3

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
Content
Loading form....