Details of Disease

General Information of Disease (ID: DISZ9QBQ)

• Disease Name: Non-syndromic ichthyosis
• Synonyms: non-syndromic ichthyosis; disorder of cornification; fish scale disease; ichthyosis (disease); DOC; fish skin disease; ichthyosis; ichthyoses
• Disease Class: EC20: Congenital ichthyosis
• Definition: Disorders of cornification that are characterized by visible scaling and/or hyperkeratosis of most or all of the skin. Inherited ichthyoses, defined as the generalized form of Mendelian disorders of cornification, affect most or all of the skin. This etiologically and phenotypically heterogenous group of conditions is caused by mutations in various different genes important for keratinocyte differentiation and epidermal barrier function. Acquired forms of ichthyosis can be observed with certain autoimmune, inflammatory, metabolic, endocrine, or infectious diseases or with malignancies.|Epidermal keratinocytes undergo a unique form of terminal differentiation and programmed cell death known as cornification. Cornification leads to the formation of the outermost skin barrier, i.e. the cornified layer, as well as to the formation of hair and nails.
• Disease Hierarchy:
  DISIDQ39: Epidermal disease
  DISZ9QBQ: Non-syndromic ichthyosis
• ICD Code:
  ICD-11: ICD-11: EC20.0Y
  Expand ICD-11: 'EC20.0Y
• Disease Identifiers:
  MONDO ID: MONDO_0019269
  MESH ID: D007057
  UMLS CUI: C0020757
  MedGen ID: 7002
  HPO ID: HP:0008064
  Orphanet ID: 79354
  SNOMED CT ID: 782957005

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
PAT-001	DMH9NAY	Phase 1	NA	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 32 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
UGCG	OTRT5P5I	Limited	Autosomal recessive	[2]
CYP4F22	OTMNPZQL	Limited	Biomarker	[17]
KRT10	OTSVRD3Q	Limited	Genetic Variation	[18]
KRT14	OTUVZ1DW	Limited	Genetic Variation	[19]
KRT16	OTGA0EQN	Limited	Altered Expression	[10]
LPIN2	OTRRTMXX	Limited	Biomarker	[3]
AP1S1	OTQ2H8DN	moderate	Biomarker	[20]
CERS3	OTKCEPYQ	moderate	Genetic Variation	[21]
CLDN1	OT27KV99	moderate	Genetic Variation	[22]
LBR	OT1HG3HG	moderate	Biomarker	[23]
MPDU1	OT27UPHN	moderate	Biomarker	[24]
SDR9C7	OTQY8SJ3	moderate	Biomarker	[25]
ABHD5	OTY829Z3	Strong	Genetic Variation	[26]
AMY2B	OTG93YV0	Strong	Genetic Variation	[27]
ANOS1	OTZJT4KN	Strong	Genetic Variation	[28]
AP1B1	OTY0K84R	Strong	Genetic Variation	[29]
AQP6	OTXS6UYY	Strong	Biomarker	[30]
ASPRV1	OT8WVIBW	Strong	Biomarker	[31]
DMKN	OTRIGZMK	Strong	Biomarker	[32]
ELOVL4	OT2M9W26	Strong	Genetic Variation	[33]
FITM2	OTED0W1S	Strong	Genetic Variation	[34]
HSD17B6	OTSB55D2	Strong	Genetic Variation	[35]
IL36B	OTYT4LP5	Strong	Biomarker	[36]
KIF22	OTY6X6BL	Strong	Biomarker	[30]
MBTPS2	OT67CC7W	Strong	Genetic Variation	[37]
MX1	OT6X8G5T	Strong	Biomarker	[38]
NLGN4X	OTDJGBK8	Strong	Genetic Variation	[28]
PNPLA2	OTR3ERMR	Strong	Biomarker	[3]
PUDP	OTEPEJLX	Strong	Genetic Variation	[28]
SNAP29	OTT30ZON	Strong	Genetic Variation	[39]
SPINK5	OT61IIAO	Strong	Genetic Variation	[40]
SUPV3L1	OT416O2G	Strong	Biomarker	[38]

This Disease Is Related to 12 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
DGAT1	TT0GV3R	Limited	Biomarker	[3]
MDM2	TT9TE0O	Limited	Therapeutic	[4]
PLIN1	TTIV27N	Limited	Genetic Variation	[3]
SLC27A4	TT20AYF	Limited	Genetic Variation	[5]
UGCG	TTPHEX3	Limited	Autosomal recessive	[2]
ALDH3A2	TTB6UM0	moderate	Genetic Variation	[6]
EBP	TT4VQZX	moderate	Genetic Variation	[7]
GJB2	TTRGZX3	moderate	Genetic Variation	[8]
ST14	TTPRO7W	moderate	Genetic Variation	[9]
IL36G	TT8SLDN	Strong	Biomarker	[10]
PNPLA6	TTWAQU2	Strong	Biomarker	[11]
SGPL1	TT618Q2	Strong	Biomarker	[12]

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
ABCA12	DT7LDG0	Limited	Genetic Variation	[13]
ABCA3	DT2T6VQ	Strong	Genetic Variation	[14]
SLC27A1	DTKDTML	Strong	Genetic Variation	[15]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
TGM5	DEW8QEH	Strong	Biomarker	[16]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] Inborn errors of cytoplasmic triglyceride metabolism.J Inherit Metab Dis. 2015 Jan;38(1):85-98. doi: 10.1007/s10545-014-9767-7. Epub 2014 Oct 10.
• [4] Identifying a hyperkeratosis signature in autosomal recessive congenital ichthyosis: Mdm2 inhibition prevents hyperkeratosis in a rat ARCI model.J Invest Dermatol. 2014 Mar;134(3):858-861. doi: 10.1038/jid.2013.374. Epub 2013 Sep 4.
• [5] A Novel SLC27A4 Splice Acceptor Site Mutation in Great Danes with Ichthyosis.PLoS One. 2015 Oct 27;10(10):e0141514. doi: 10.1371/journal.pone.0141514. eCollection 2015.
• [6] Genotype and phenotype variability in Sjgren-Larsson syndrome.Hum Mutat. 2019 Feb;40(2):177-186. doi: 10.1002/humu.23679. Epub 2018 Nov 26.
• [7] Conradi-Hnermann-Happle syndrome: a novel heterozygous missense mutation, c.204G>T (p.W68C).Pediatr Dermatol. 2014 Jul-Aug;31(4):493-6. doi: 10.1111/pde.12336. Epub 2014 Jun 11.
• [8] Overview of skin diseases linked to connexin gene mutations.Int J Dermatol. 2014 Feb;53(2):192-205. doi: 10.1111/ijd.12062. Epub 2013 May 15.
• [9] A novel mutation in ST14 at a functionally significant amino acid residue expands the spectrum of ichthyosis-hypotrichosis syndrome.Orphanet J Rare Dis. 2017 Dec 6;12(1):176. doi: 10.1186/s13023-017-0728-8.
• [10] An IL-17-dominant immune profile is shared across the major orphan forms of ichthyosis.J Allergy Clin Immunol. 2017 Jan;139(1):152-165. doi: 10.1016/j.jaci.2016.07.019. Epub 2016 Aug 20.
• [11] The clinical spectrum of inherited diseases involved in the synthesis and remodeling of complex lipids. A tentative overview.J Inherit Metab Dis. 2015 Jan;38(1):19-40. doi: 10.1007/s10545-014-9776-6. Epub 2014 Nov 21.
• [12] Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency. J Clin Invest. 2017 Mar 1;127(3):912-928. doi: 10.1172/JCI89626. Epub 2017 Feb 6.
• [13] Unknown mutations and genotype/phenotype correlations of autosomal recessive congenital ichthyosis in patients from Saudi Arabia and Pakistan.Mol Genet Genomic Med. 2019 Mar;7(3):e539. doi: 10.1002/mgg3.539. Epub 2019 Jan 1.
• [14] Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer. J Clin Invest. 2005 Jul;115(7):1777-84. doi: 10.1172/JCI24834.
• [15] Fatty acid transport proteins, implications in physiology and disease.Biochim Biophys Acta. 2012 May;1821(5):852-7. doi: 10.1016/j.bbalip.2011.09.010. Epub 2011 Sep 25.
• [16] Expression of transglutaminase 5 in normal and pathologic human epidermis.J Invest Dermatol. 2002 Sep;119(3):670-7. doi: 10.1046/j.1523-1747.2002.01853.x.
• [17] Severe Skin Permeability Barrier Dysfunction inKnockout Mice Deficient in a Fatty Acid -Hydroxylase Crucial to Acylceramide Production.J Invest Dermatol. 2020 Feb;140(2):319-326.e4. doi: 10.1016/j.jid.2019.07.689. Epub 2019 Jul 26.
• [18] Coexistence of mutations in keratin 10 (KRT10) and the mitochondrial genome in a patient with ichthyosis with confetti and Leber's hereditary optic neuropathy.Am J Med Genet A. 2017 Nov;173(11):3093-3097. doi: 10.1002/ajmg.a.38403. Epub 2017 Sep 25.
• [19] Disease-linked connexin26 S17F promotes volar skin abnormalities and mild wound healing defects in mice.Cell Death Dis. 2017 Jun 1;8(6):e2845. doi: 10.1038/cddis.2017.234.
• [20] An atypical form of erythrokeratodermia variabilis maps to chromosome 7q22. Hum Genet. 2005 Feb;116(3):167-71. doi: 10.1007/s00439-004-1193-8. Epub 2004 Nov 25.
• [21] Autosomal recessive congenital ichthyosis: CERS3 mutations identified by a next generation sequencing panel targeting ichthyosis genes.Eur J Hum Genet. 2017 Nov;25(11):1282-1285. doi: 10.1038/ejhg.2017.137. Epub 2017 Sep 6.
• [22] Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. Gastroenterology. 2004 Nov;127(5):1386-90. doi: 10.1053/j.gastro.2004.07.022.
• [23] HEM dysplasia and ichthyosis are likely laminopathies and not due to 3beta-hydroxysterol Delta14-reductase deficiency.Hum Mol Genet. 2007 May 15;16(10):1176-87. doi: 10.1093/hmg/ddm065. Epub 2007 Apr 2.
• [24] Severe ichthyosis in MPDU1-CDG.J Inherit Metab Dis. 2018 Nov;41(6):1293-1294. doi: 10.1007/s10545-018-0189-9. Epub 2018 May 2.
• [25] SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation.J Clin Invest. 2020 Feb 3;130(2):890-903. doi: 10.1172/JCI130675.
• [26] Neutral Lipid Storage Diseases as Cellular Model to Study Lipid Droplet Function. Cells. 2019 Feb 21;8(2):187. doi: 10.3390/cells8020187.
• [27] Hepoxilin A3 (HXA3) synthase deficiency is causative of a novel ichthyosis form.FEBS Lett. 2008 Jan 23;582(2):279-85. doi: 10.1016/j.febslet.2007.12.017. Epub 2007 Dec 18.
• [28] Expanding the genetic spectrum of ANOS1 mutations in patients with congenital hypogonadotropic hypogonadism.Hum Reprod. 2017 Mar 1;32(3):704-711. doi: 10.1093/humrep/dew354.
• [29] Recessive Mutations in AP1B1 Cause Ichthyosis, Deafness, and Photophobia. Am J Hum Genet. 2019 Nov 7;105(5):1023-1029. doi: 10.1016/j.ajhg.2019.09.021. Epub 2019 Oct 17.
• [30] Neurotological and neuroanatomical changes in the connexin-26-related HID/KID syndrome.Audiol Neurootol. 2006;11(4):242-8. doi: 10.1159/000093110. Epub 2006 May 4.
• [31] A de novo variant in the ASPRV1 gene in a dog with ichthyosis.PLoS Genet. 2017 Mar 1;13(3):e1006651. doi: 10.1371/journal.pgen.1006651. eCollection 2017 Mar.
• [32] Homeostatic Function of Dermokine in the Skin Barrier and Inflammation.J Invest Dermatol. 2020 Apr;140(4):838-849.e9. doi: 10.1016/j.jid.2019.09.011. Epub 2019 Oct 25.
• [33] ELOVL4: Very long-chain fatty acids serve an eclectic role in mammalian health and function.Prog Retin Eye Res. 2019 Mar;69:137-158. doi: 10.1016/j.preteyeres.2018.10.004. Epub 2018 Oct 25.
• [34] A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy. Dis Model Mech. 2017 Feb 1;10(2):105-118. doi: 10.1242/dmm.026476. Epub 2016 Dec 15.
• [35] Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3. Hum Mol Genet. 2006 Mar 1;15(5):767-76. doi: 10.1093/hmg/ddi491. Epub 2006 Jan 25.
• [36] Ichthyosis molecular fingerprinting shows profound T(H)17 skewing and a unique barrier genomic signature.J Allergy Clin Immunol. 2019 Feb;143(2):604-618. doi: 10.1016/j.jaci.2018.03.021. Epub 2018 May 24.
• [37] Recurrent splice-site mutation in MBTPS2 underlying IFAP syndrome with Olmsted syndrome-like features in a Chinese patient.Clin Exp Dermatol. 2014 Mar;39(2):158-61. doi: 10.1111/ced.12248. Epub 2013 Dec 7.
• [38] Disruption of Supv3L1 damages the skin and causes sarcopenia, loss of fat, and death.Mamm Genome. 2009 Feb;20(2):92-108. doi: 10.1007/s00335-008-9168-z. Epub 2009 Jan 15.
• [39] CEDNIK syndrome results from loss-of-function mutations in SNAP29. Br J Dermatol. 2011 Mar;164(3):610-6. doi: 10.1111/j.1365-2133.2010.10133.x. Epub 2011 Feb 17.
• [40] Activography reveals aberrant proteolysis in desquamating diseases of differing backgrounds.Exp Dermatol. 2019 Jan;28(1):86-89. doi: 10.1111/exd.13832.