Details of Disease

General Information of Disease (ID: DISATMDB)

• Disease Name: Wiskott-Aldrich syndrome
• Synonyms: eczema thrombocytopenia immunodeficiency syndrome; Aldrich syndrome; Imd 2; immunodeficiency 2; Wiskott-Aldrich syndrome, X-linked recessive; WAS; Wiskott Aldrich syndrome; Wiskott-Aldrich syndrome; Wiskott syndrome; Wiskott-Aldrich syndrome 1; eczema-thrombocytopenia-immunodeficiency syndrome
• Disease Class: 3B62: Qualitative platelet defect
• Definition: Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disease characterized by microthrombocytopenia, eczema, infections and an increased risk for autoimmune manifestations and malignancies.
• Disease Hierarchy:
  DISGXLG5: Hereditary neoplastic syndrome
  DIS1DL2M: Inherited blood coagulation disorder
  DIS3PN9X: X-linked disease
  DISKR6QJ: Combined immunodeficiency
  DISATMDB: Wiskott-Aldrich syndrome
• ICD Code:
  ICD-11: ICD-11: 3B62.0
  ICD-10: ICD-10: D82.0
  Expand ICD-11: '3B62.0
  Expand ICD-10: 'D82.0
• Disease Identifiers:
  MONDO ID: MONDO_0010518
  MESH ID: D014923
  UMLS CUI: C0043194
  OMIM ID: 301000
  MedGen ID: 21921
  Orphanet ID: 906
  SNOMED CT ID: 36070007

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 6 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
OTL-103	DM3BK2Y	Phase 3	Gene therapy	[1]
Drug 2696275	DMVXUG2	Phase 2	NA	[2]
GSK2696275	DM5CCMX	Phase 2	NA	[3]
Hematopoietic stem cell gene therapy	DMQWI7V	Phase 1/2	NA	[4]
WAS gene therapy	DMABB3S	Phase 1/2	NA	[5]
WASP gene therapy	DMN62MP	Phase 1/2	NA	[5]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 19 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
WIPF1	OTWZO0DW	Supportive	Autosomal dominant	[6]
WAS	OTD03E8M	Definitive	X-linked	[7]
ANGPTL2	OTB6JG41	moderate	Biomarker	[9]
PSMA7	OTPHI6ST	moderate	Genetic Variation	[10]
ACTR2	OT3C8U5T	Strong	Biomarker	[9]
ACTR3	OT05LJSH	Strong	Biomarker	[18]
ARPC1B	OTYE3DN2	Strong	Biomarker	[19]
CCNDBP1	OTBWG1M0	Strong	Biomarker	[9]
DOCK8	OTNQLL21	Strong	Biomarker	[20]
IL2RG	OTRZ3OMY	Strong	Biomarker	[21]
INTS8	OT3SRRLM	Strong	Genetic Variation	[22]
LY6E	OTMG16BZ	Strong	Biomarker	[23]
NCKAP1L	OTADCEUK	Strong	Biomarker	[24]
NCKIPSD	OT24UORN	Strong	Biomarker	[9]
NELFCD	OTOLTZPU	Strong	Genetic Variation	[25]
NOL3	OT1K0L0D	Strong	Genetic Variation	[26]
TBC1D25	OT11OABF	Strong	Genetic Variation	[27]
TFE3	OTM99ZWH	Strong	Biomarker	[28]
FUT1	OTODG57A	Definitive	Biomarker	[29]

This Disease Is Related to 10 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SPN	TTOZAX0	Limited	Biomarker	[8]
AICDA	TTKRTP6	moderate	Biomarker	[9]
ADA	TTLP57V	Strong	Biomarker	[10]
FCER2	TTCH6MU	Strong	Altered Expression	[11]
FOXP3	TT1X3QF	Strong	Genetic Variation	[12]
HAX1	TT21BYA	Strong	Genetic Variation	[13]
NCK1	TTMA3VF	Strong	Biomarker	[14]
OTC	TT5KIO9	Strong	Biomarker	[15]
TBX21	TTNF9PH	Strong	Altered Expression	[16]
WAS	TTE8T73	Definitive	X-linked	[7]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
G6PC3	DEE1B8O	Strong	Genetic Variation	[17]

References

• [1] ClinicalTrials.gov (NCT03837483) A Clinical Study to Evaluate the Use of a Cryopreserved Formulation of OTL-103 in Subjects With Wiskott-Aldrich Syndrome. U.S. National Institutes of Health.
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800042616)
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] ClinicalTrials.gov (NCT02559830) Autologous Hematopoietic Stem Cell Gene Therapy for Metachromatic Leukodystrophy and Adrenoleukodystrophy.
• [5] ClinicalTrials.gov (NCT01347242) Gene Therapy for Wiskott-Aldrich Syndrome (WAS). U.S. National Institutes of Health.
• [6] A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP. J Exp Med. 2012 Jan 16;209(1):29-34. doi: 10.1084/jem.20110896. Epub 2012 Jan 9.
• [7] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [8] IgA nephropathy associated with X-linked thrombocytopenia.Am J Kidney Dis. 2004 Mar;43(3):e7-12. doi: 10.1053/j.ajkd.2003.11.016.
• [9] Single-Turnover Activation of Arp2/3 Complex by Dip1 May Balance Nucleation of Linear versus Branched Actin Filaments.Curr Biol. 2019 Oct 7;29(19):3331-3338.e7. doi: 10.1016/j.cub.2019.08.023. Epub 2019 Sep 26.
• [10] Bone marrow harvesting from paediatric patients undergoing haematopoietic stem cell gene therapy.Bone Marrow Transplant. 2019 Dec;54(12):1995-2003. doi: 10.1038/s41409-019-0573-6. Epub 2019 May 31.
• [11] Defective expression of CD23 and autocrine growth-stimulation in Epstein-Barr virus (EBV)-transformed B cells from patients with Wiskott-Aldrich syndrome (WAS).Clin Exp Immunol. 1993 Jan;91(1):43-9. doi: 10.1111/j.1365-2249.1993.tb03351.x.
• [12] Lambert-Eaton myasthenic syndrome in a 13-year-old girl with Xp11.22-p11.23 duplication.Eur J Paediatr Neurol. 2014 May;18(3):439-43. doi: 10.1016/j.ejpn.2014.01.001. Epub 2014 Jan 15.
• [13] Homozygous HAX1 mutations in severe congenital neutropenia patients with sporadic disease: a novel mutation in two unrelated British kindreds.Br J Haematol. 2009 Mar;144(5):762-70. doi: 10.1111/j.1365-2141.2008.07493.x. Epub 2008 Nov 22.
• [14] Activation of Wiskott-Aldrich syndrome protein and its association with other proteins by stromal cell-derived factor-1alpha is associated with cell migration in a T-lymphocyte line.Exp Hematol. 2002 Jul;30(7):761-6. doi: 10.1016/s0301-472x(02)00823-8.
• [15] Genetic mapping of the Wiskott-Aldrich syndrome with two highly-linked polymorphic DNA markers.Genomics. 1988 Jul;3(1):39-43. doi: 10.1016/0888-7543(88)90156-5.
• [16] Nuclear role of WASp in the pathogenesis of dysregulated TH1 immunity in human Wiskott-Aldrich syndrome.Sci Transl Med. 2010 Jun 23;2(37):37ra44. doi: 10.1126/scitranslmed.3000813.
• [17] Genetic etiologies of severe congenital neutropenia.Curr Opin Pediatr. 2011 Feb;23(1):21-6. doi: 10.1097/MOP.0b013e32834262f8.
• [18] Motility determinants in WASP family proteins.Mol Biol Cell. 2002 Nov;13(11):4045-59. doi: 10.1091/mbc.e02-05-0294.
• [19] Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease.Nat Commun. 2017 Apr 3;8:14816. doi: 10.1038/ncomms14816.
• [20] Wiskott-Aldrich Syndrome (WAS) and Dedicator of Cytokinesis 8- (DOCK8) Deficiency.Front Pediatr. 2019 Nov 5;7:451. doi: 10.3389/fped.2019.00451. eCollection 2019.
• [21] Lentiviral vectors for the treatment of primary immunodeficiencies.J Inherit Metab Dis. 2014 Jul;37(4):525-33. doi: 10.1007/s10545-014-9690-y. Epub 2014 Mar 12.
• [22] Clinical aspects and genetic analysis of taiwanese patients with wiskott-Aldrich syndrome protein mutation: the first identification of x-linked thrombocytopenia in the chinese with novel mutations.J Clin Immunol. 2010 Jul;30(4):593-601. doi: 10.1007/s10875-010-9381-x. Epub 2010 Mar 16.
• [23] Rickettsia Sca2 Recruits Two Actin Subunits for Nucleation but Lacks WH2 Domains.Biophys J. 2019 Feb 5;116(3):540-550. doi: 10.1016/j.bpj.2018.12.009. Epub 2018 Dec 18.
• [24] The Wave2 scaffold Hem-1 is required for transition of fetal liver hematopoiesis to bone marrow.Nat Commun. 2018 Jun 18;9(1):2377. doi: 10.1038/s41467-018-04716-5.
• [25] Disruption of hSWI/SNF complexes in T cells by WAS mutations distinguishes X-linked thrombocytopenia from Wiskott-Aldrich syndrome.Blood. 2014 Nov 27;124(23):3409-19. doi: 10.1182/blood-2014-07-587642. Epub 2014 Sep 24.
• [26] Mixed chimera status of 12 patients with Wiskott-Aldrich syndrome (WAS) after hematopoietic stem cell transplantation: evaluation by flow cytometric analysis of intracellular WAS protein expression.Blood. 2002 Aug 15;100(4):1208-14. doi: 10.1182/blood-2002-01-0211.
• [27] A high-resolution map of genes, microsatellite markers, and new dinucleotide repeats from UBE1 to the GATA locus in the region Xp11.23.Genomics. 1995 Sep 1;29(1):247-52. doi: 10.1006/geno.1995.1238.
• [28] Linkage of Wiskott-Aldrich syndrome with three marker loci, DXS426, SYP and TFE3, which map to the Xp11.3-p11.22 region.Hum Genet. 1993 Oct 1;92(3):250-3. doi: 10.1007/BF00244467.
• [29] Outcomes following gene therapy in patients with severe Wiskott-Aldrich syndrome.JAMA. 2015 Apr 21;313(15):1550-63. doi: 10.1001/jama.2015.3253.