ARCI6
MCID: ICH042
MIFTS: 30

Ichthyosis, Congenital, Autosomal Recessive 6 (ARCI6)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Ichthyosis, Congenital, Autosomal Recessive 6

MalaCards integrated aliases for Ichthyosis, Congenital, Autosomal Recessive 6:

Name: Ichthyosis, Congenital, Autosomal Recessive 6 57 74 13 72
Autosomal Recessive Congenital Ichthyosis 6 12 29 6
Arci6 57 12 74
Ichthyosis, Congenital, Autosomal Recessive, Nipal4-Related 57 74
Ichthyosis, Congenital, Autosomal Recessive, Ichthyin-Related 74
Ichthyosis, Congenital, Autosomal Recessive, Type 6 40
Ichthyosis Congenital Autosomal Recessive 74

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
severity of skin symptoms may vary within families
some patients report cyclical changes in severity of symptoms


HPO:

32
ichthyosis, congenital, autosomal recessive 6:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0060715
MeSH 44 D017490
ICD10 33 Q80.2
MedGen 42 C2677065
UMLS 72 C2677065

Summaries for Ichthyosis, Congenital, Autosomal Recessive 6

OMIM : 57 Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (summary by Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI4B; 242500) (Oji et al., 2010). NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (summary by Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to a reduced barrier function and defects of lipid composition in the stratum corneum (summary by Lefevre et al., 2006). In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (summary by Eckl et al., 2005). For a general phenotypic description and discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300). (612281)

MalaCards based summary : Ichthyosis, Congenital, Autosomal Recessive 6, also known as autosomal recessive congenital ichthyosis 6, is related to ichthyosis, congenital, autosomal recessive 2 and ichthyosis, congenital, autosomal recessive 1. An important gene associated with Ichthyosis, Congenital, Autosomal Recessive 6 is NIPAL4 (NIPA Like Domain Containing 4). Affiliated tissues include skin, and related phenotypes are hypohidrosis and ectropion

Disease Ontology : 12 An autosomal recessive congenital ichthyosis characterized by generalized ichthyosis, hyperkeratosis, parakeratosis and moderate acanthosis that has material basis in homozygous or compound heterozygous mutation in the NIPAL4 gene on chromosome 5q33.

UniProtKB/Swiss-Prot : 74 Ichthyosis, congenital, autosomal recessive 6: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs.

Related Diseases for Ichthyosis, Congenital, Autosomal Recessive 6

Diseases in the Ichthyosis family:

Ichthyosis, Congenital, Autosomal Recessive 2 Ichthyosis, Congenital, Autosomal Recessive 1
Ichthyosis, Congenital, Autosomal Recessive 4b Ichthyosis, Congenital, Autosomal Recessive 4a
Ichthyosis, Congenital, Autosomal Recessive 11 Ichthyosis, Congenital, Autosomal Recessive 5
Ichthyosis, Congenital, Autosomal Recessive 3 Ichthyosis, Congenital, Autosomal Recessive 6
Ichthyosis, Congenital, Autosomal Recessive 8 Ichthyosis, Congenital, Autosomal Recessive 7
Ichthyosis, Congenital, Autosomal Recessive 9 Ichthyosis, Congenital, Autosomal Recessive 10
Ichthyosis, Congenital, Autosomal Recessive 12 Ichthyosis, Congenital, Autosomal Recessive 14
Ichthyosis, Congenital, Autosomal Recessive 13 Autosomal Recessive Congenital Ichthyosis
Ichthyosis, Acquired Inherited Ichthyosis
Autosomal Ichthyosis Syndrome

Diseases related to Ichthyosis, Congenital, Autosomal Recessive 6 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 15)
# Related Disease Score Top Affiliating Genes
1 ichthyosis, congenital, autosomal recessive 2 12.7
2 ichthyosis, congenital, autosomal recessive 1 12.7
3 ichthyosis, congenital, autosomal recessive 3 12.7
4 ichthyosis, congenital, autosomal recessive 8 12.7
5 ichthyosis, congenital, autosomal recessive 9 12.7
6 ichthyosis, congenital, autosomal recessive 10 12.7
7 ichthyosis, congenital, autosomal recessive 4b 12.6
8 ichthyosis, congenital, autosomal recessive 4a 12.6
9 ichthyosis, congenital, autosomal recessive 11 12.6
10 ichthyosis, congenital, autosomal recessive 5 12.6
11 ichthyosis, congenital, autosomal recessive 12 12.6
12 ichthyosis, congenital, autosomal recessive 14 12.6
13 ichthyosis, congenital, autosomal recessive 13 12.6
14 ichthyosis, congenital, autosomal recessive 7 12.4
15 autosomal recessive congenital ichthyosis 11.3

Graphical network of the top 20 diseases related to Ichthyosis, Congenital, Autosomal Recessive 6:



Diseases related to Ichthyosis, Congenital, Autosomal Recessive 6

Symptoms & Phenotypes for Ichthyosis, Congenital, Autosomal Recessive 6

Human phenotypes related to Ichthyosis, Congenital, Autosomal Recessive 6:

32 (show all 7)
# Description HPO Frequency HPO Source Accession
1 hypohidrosis 32 occasional (7.5%) HP:0000966
2 ectropion 32 occasional (7.5%) HP:0000656
3 erythroderma 32 occasional (7.5%) HP:0001019
4 palmoplantar keratoderma 32 HP:0000982
5 parakeratosis 32 HP:0001036
6 epidermal acanthosis 32 HP:0025092
7 congenital nonbullous ichthyosiform erythroderma 32 HP:0007479

Symptoms via clinical synopsis from OMIM:

57
Skin Nails Hair Skin Histology:
hyperkeratosis
parakeratosis
acanthosis, moderate
orthohyperkeratosis (in some patients)
thickening of stratum corneum
more
Head And Neck Eyes:
ectropion (in some patients)

Skin Nails Hair Nails:
clubbing of nails (in some patients)

Skin Nails Hair Skin:
palmoplantar keratoderma
collodion membrane at birth (in some patients)
hypohidrosis (in some patients)
erythroderma (in some patients)
icthyosis, generalized
more
Skin Nails Hair Skin Electron Microscopy:
lamellae in stratum corneum with few or minimal lipid droplets
regularly elongated perinuclear membranes in stratum corneum and granulosum
vesicular complexes in stratum corneum
electron-lucent vacuoles, some containing 1 or more smaller vesicles

Clinical features from OMIM:

612281

Drugs & Therapeutics for Ichthyosis, Congenital, Autosomal Recessive 6

Search Clinical Trials , NIH Clinical Center for Ichthyosis, Congenital, Autosomal Recessive 6

Genetic Tests for Ichthyosis, Congenital, Autosomal Recessive 6

Genetic tests related to Ichthyosis, Congenital, Autosomal Recessive 6:

# Genetic test Affiliating Genes
1 Autosomal Recessive Congenital Ichthyosis 6 29 NIPAL4

Anatomical Context for Ichthyosis, Congenital, Autosomal Recessive 6

MalaCards organs/tissues related to Ichthyosis, Congenital, Autosomal Recessive 6:

41
Skin

Publications for Ichthyosis, Congenital, Autosomal Recessive 6

Articles related to Ichthyosis, Congenital, Autosomal Recessive 6:

# Title Authors PMID Year
1
Congenital ichthyosis: mutations in ichthyin are associated with specific structural abnormalities in the granular layer of epidermis. 8 71
17557927 2007
2
Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis. 8 71
15317751 2004
3
Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Sorèze 2009. 8
20643494 2010
4
Autosomal recessive congenital ichthyosis. 8
19434086 2009
5
Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. 8
16436457 2006
6
Mutation spectrum and functional analysis of epidermis-type lipoxygenases in patients with autosomal recessive congenital ichthyosis. 8
16116617 2005
7
The clinical spectrum of nonbullous congenital ichthyosiform erythroderma and lamellar ichthyosis. 8
12780701 2003
8
Autosomal Recessive Congenital Ichthyosis 71
20301593 2001
9
Two new loci for autosomal recessive ichthyosis on chromosomes 3p21 and 19p12-q12 and evidence for further genetic heterogeneity. 8
10712205 2000

Variations for Ichthyosis, Congenital, Autosomal Recessive 6

ClinVar genetic disease variations for Ichthyosis, Congenital, Autosomal Recessive 6:

6 (show all 28)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 NIPAL4 NM_001099287.1(NIPAL4): c.688G> A (p.Gly230Arg) single nucleotide variant Pathogenic rs370356566 5:156898741-156898741 5:157471733-157471733
2 NIPAL4 NM_001099287.1(NIPAL4): c.433C> T (p.Arg145Ter) single nucleotide variant Pathogenic rs199422216 5:156890311-156890311 5:157463303-157463303
3 NIPAL4 NIPAL4, ALA114ASN single nucleotide variant Pathogenic
4 NIPAL4 NM_001099287.1(NIPAL4): c.527C> A (p.Ala176Asp) single nucleotide variant Pathogenic rs199422217 5:156895736-156895736 5:157468728-157468728
5 NIPAL4 NM_001099287.1(NIPAL4): c.772+1G> A single nucleotide variant Pathogenic 5:156898826-156898826 5:157471818-157471818
6 NIPAL4 NM_001099287.1(NIPAL4): c.706_712del (p.Ile236fs) deletion Pathogenic 5:156898759-156898765 5:157471751-157471757
7 NIPAL4 NM_001099287.1(NIPAL4): c.1083C> A (p.Tyr361Ter) single nucleotide variant Pathogenic 5:156899650-156899650 5:157472642-157472642
8 NIPAL4 NM_001099287.1(NIPAL4): c.2T> C (p.Met1Thr) single nucleotide variant Pathogenic 5:156887144-156887144 5:157460136-157460136
9 NIPAL4 NM_001099287.1(NIPAL4): c.283del (p.Leu95fs) deletion Pathogenic 5:156890161-156890161 5:157463153-157463153
10 NIPAL4 NM_001099287.1(NIPAL4): c.407T> A (p.Val136Asp) single nucleotide variant Pathogenic 5:156890285-156890285 5:157463277-157463277
11 NIPAL4 NM_001099287.1(NIPAL4): c.425G> T (p.Gly142Val) single nucleotide variant Pathogenic 5:156890303-156890303 5:157463295-157463295
12 NIPAL4 NM_001099287.1(NIPAL4): c.470G> A (p.Gly157Glu) single nucleotide variant Pathogenic 5:156894063-156894063 5:157467055-157467055
13 NIPAL4 NM_001099287.1(NIPAL4): c.534A> C (p.Glu178Asp) single nucleotide variant Pathogenic 5:156895743-156895743 5:157468735-157468735
14 NIPAL4 NM_001099287.1(NIPAL4): c.555C> G (p.Tyr185Ter) single nucleotide variant Pathogenic 5:156895764-156895764 5:157468756-157468756
15 NIPAL4 NM_001099287.1(NIPAL4): c.623C> T (p.Ser208Phe) single nucleotide variant Pathogenic 5:156898676-156898676 5:157471668-157471668
16 NIPAL4 NM_001099287.1(NIPAL4): c.695C> G (p.Thr232Arg) single nucleotide variant Pathogenic 5:156898748-156898748 5:157471740-157471740
17 NIPAL4 NM_001099287.1(NIPAL4): c.709del (p.His237fs) deletion Pathogenic 5:156898762-156898762 5:157471754-157471754
18 NIPAL4 NM_001099287.1(NIPAL4): c.709C> G (p.His237Asp) single nucleotide variant Pathogenic 5:156898762-156898762 5:157471754-157471754
19 NIPAL4 NM_001099287.1(NIPAL4): c.836C> T (p.Pro279Leu) single nucleotide variant Pathogenic 5:156899403-156899403 5:157472395-157472395
20 NIPAL4 NM_001099287.1(NIPAL4): c.844G> A (p.Gly282Arg) single nucleotide variant Pathogenic 5:156899411-156899411 5:157472403-157472403
21 NIPAL4 NM_001099287.1(NIPAL4): c.889G> A (p.Gly297Arg) single nucleotide variant Pathogenic 5:156899456-156899456 5:157472448-157472448
22 NIPAL4 NM_001099287.1(NIPAL4): c.939C> G (p.Asn313Lys) single nucleotide variant Pathogenic 5:156899506-156899506 5:157472498-157472498
23 NIPAL4 NM_001099287.1(NIPAL4): c.1014C> A (p.Ser338Arg) single nucleotide variant Pathogenic 5:156899581-156899581 5:157472573-157472573
24 NIPAL4 NM_001099287.1(NIPAL4): c.1268del (p.Asn423fs) deletion Pathogenic 5:156899835-156899835 5:157472827-157472827
25 NIPAL4 NM_001099287.1(NIPAL4): c.223+5G> C single nucleotide variant Pathogenic 5:156887370-156887370 5:157460362-157460362
26 NIPAL4 NM_001099287.1(NIPAL4): c.463+5G> A single nucleotide variant Pathogenic 5:156890346-156890346 5:157463338-157463338
27 NIPAL4 NM_001099287.1(NIPAL4): c.611+1G> A single nucleotide variant Pathogenic 5:156895821-156895821 5:157468813-157468813
28 NIPAL4 NM_001099287.1(NIPAL4): c.612-3del deletion Pathogenic 5:156898662-156898662 5:157471654-157471654

UniProtKB/Swiss-Prot genetic disease variations for Ichthyosis, Congenital, Autosomal Recessive 6:

74
# Symbol AA change Variation ID SNP ID
1 NIPAL4 p.Gly142Val VAR_031736 rs775903553
2 NIPAL4 p.Ala176Asp VAR_031737 rs199422217
3 NIPAL4 p.Ser208Phe VAR_031738
4 NIPAL4 p.His237Asn VAR_031739
5 NIPAL4 p.Gly297Arg VAR_031740 rs375688767
6 NIPAL4 p.Gly230Arg VAR_054120 rs370356566
7 NIPAL4 p.Ser135Arg VAR_075461 rs376803325

Expression for Ichthyosis, Congenital, Autosomal Recessive 6

Search GEO for disease gene expression data for Ichthyosis, Congenital, Autosomal Recessive 6.

Pathways for Ichthyosis, Congenital, Autosomal Recessive 6

GO Terms for Ichthyosis, Congenital, Autosomal Recessive 6

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