Details of Disease

General Information of Disease (ID: DISW6GL2)

• Disease Name: Cockayne syndrome
• Synonyms: progeroid nanism; progeria-like syndrome; dwarfism-retinal atrophy-deafness syndrome; Cockayne's syndrome; Neill-Dingwall syndrome
• Disease Class: LD2B: Premature ageing appearance
• Definition: A multisystem condition characterized by short stature, a characteristic facial appearance, premature aging, photosensitivity, progressive neurological dysfunction, and intellectual deficit.
• Disease Hierarchy:
  DISCPWH9: Autosomal recessive disease
  DISMFQKM: Developmental anomaly of metabolic origin
  DISSLPEK: Progeroid syndrome
  DISN7YWO: DNA repair disease
  DISW6GL2: Cockayne syndrome
• ICD Code:
  ICD-11: ICD-11: LD2B
  ICD-10: ICD-10: Q75.5, Q87.8
  Expand ICD-11: 'LD2B
  Expand ICD-10: 'Q75.5; 'Q87.8
• Disease Identifiers:
  MONDO ID: MONDO_0016006
  MESH ID: D003057
  UMLS CUI: C0009207
  MedGen ID: 40363
  Orphanet ID: 191
  SNOMED CT ID: 21086008

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
Prodarsan	DMC8M1R	Phase 1/2	NA	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
NR1H2	TTXA6PH	Limited	Biomarker	[2]
XPA	TTGT87E	Limited	Biomarker	[3]
CDCA8	TT04YCM	Strong	Genetic Variation	[4]
PTPN11	TT7WUAV	Strong	Biomarker	[5]
RAF1	TTAN5W2	Strong	Biomarker	[6]
WRN	TT2H5WQ	Strong	Genetic Variation	[7]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
B4GALT7	DEKRS6L	Strong	Genetic Variation	[8]

This Disease Is Related to 26 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ERCC2	OT1C8HQ4	Limited	Biomarker	[9]
ERCC3	OTVAW3P1	Limited	Biomarker	[9]
GTF2H1	OTCRXC6B	Limited	Biomarker	[9]
GTF2H2	OTK72L9I	Limited	Biomarker	[9]
GTF2H3	OT87W5QJ	Limited	Biomarker	[9]
GTF2H5	OTRL219S	Limited	Biomarker	[9]
SPRTN	OT01D5CE	Limited	Genetic Variation	[10]
BANF1	OTP7Z38L	moderate	Genetic Variation	[11]
BTN2A2	OTUOAJZA	Strong	Genetic Variation	[12]
ENDOV	OTX2GXXX	Strong	Biomarker	[13]
ERCC4	OTFIOPG1	Strong	Biomarker	[14]
ERCC5	OTQAKFJM	Strong	Biomarker	[15]
EYA1	OTHU807A	Strong	Genetic Variation	[4]
GTF2H4	OTPD1DIU	Strong	Biomarker	[9]
GYPB	OTESHUIX	Strong	Biomarker	[16]
GYPE	OTBHAG6A	Strong	Biomarker	[16]
HFM1	OTHV3EFE	Strong	Genetic Variation	[17]
HTRA3	OTXJ0H4X	Strong	Genetic Variation	[18]
LZTR1	OTIDM6XO	Strong	Biomarker	[19]
NEFM	OT8VCBNF	Strong	Biomarker	[20]
POLR3A	OT5MSK10	Strong	Genetic Variation	[21]
PYCR1	OTQHB52T	Strong	Genetic Variation	[22]
RAD52	OT0OTDHI	Strong	Biomarker	[23]
RIT1	OTVNOGOH	Strong	Biomarker	[24]
SOS1	OTTCWXC3	Strong	Biomarker	[25]
SYT9	OT7S8WU0	Strong	Biomarker	[26]

References

• [1] ClinicalTrials.gov (NCT01142154) Pharmacokinetics and Safety Study of Single and Multiple Oral Doses Prodarsan in Patients With Cockayne Syndrome. U.S. National Institutes of Health.
• [2] What happens at the lesion does not stay at the lesion: Transcription-coupled nucleotide excision repair and the effects of DNA damage on transcription in cis and trans.DNA Repair (Amst). 2018 Nov;71:56-68. doi: 10.1016/j.dnarep.2018.08.007. Epub 2018 Aug 23.
• [3] Von Hippel-Lindau-coupled and transcription-coupled nucleotide excision repair-dependent degradation of RNA polymerase II in response to trabectedin.Clin Cancer Res. 2008 Oct 15;14(20):6449-55. doi: 10.1158/1078-0432.CCR-08-0730.
• [4] Abnormal sensitivity of some Cockayne's syndrome cell strains to UV- and gamma-rays. Association with a reduced ability to repair potentially lethal damage.Mutat Res. 1984 Feb;131(2):61-70. doi: 10.1016/0167-8817(84)90012-9.
• [5] Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation.Nat Med. 2004 Aug;10(8):849-57. doi: 10.1038/nm1084. Epub 2004 Jul 25.
• [6] Increased BRAF heterodimerization is the common pathogenic mechanism for noonan syndrome-associated RAF1 mutants.Mol Cell Biol. 2012 Oct;32(19):3872-90. doi: 10.1128/MCB.00751-12. Epub 2012 Jul 23.
• [7] Recent Trends in WRN Gene Mutation Patterns in Individuals with Werner Syndrome.J Am Geriatr Soc. 2017 Aug;65(8):1853-1856. doi: 10.1111/jgs.14906. Epub 2017 Apr 10.
• [8] Defective glycosaminoglycan substitution of decorin in a patient with progeroid syndrome is a direct consequence of two point mutations in the galactosyltransferase I (beta4GalT-7) gene.Biochem Genet. 2005 Feb;43(1-2):65-77. doi: 10.1007/s10528-005-1068-2.
• [9] Transcription preinitiation complex structure and dynamics provide insight into genetic diseases.Nat Struct Mol Biol. 2019 Jun;26(6):397-406. doi: 10.1038/s41594-019-0220-3. Epub 2019 May 20.
• [10] SPRTN is a new player in an old story.Nat Genet. 2014 Nov;46(11):1155-7. doi: 10.1038/ng.3125.
• [11] Barrier to Autointegration Factor (BANF1): interwoven roles in nuclear structure, genome integrity, innate immunity, stress responses and progeria.Curr Opin Cell Biol. 2015 Jun;34:61-8. doi: 10.1016/j.ceb.2015.05.006. Epub 2015 Jun 10.
• [12] DNA repair helicase: a component of BTF2 (TFIIH) basic transcription factor.Science. 1993 Apr 2;260(5104):58-63. doi: 10.1126/science.8465201.
• [13] Incomplete complementation of the DNA repair defect in cockayne syndrome cells by the denV gene from bacteriophage T4 suggests a deficiency in base excision repair.Mutat Res. 1997 Oct;385(1):59-74. doi: 10.1016/s0921-8777(97)00039-6.
• [14] Repair protein persistence at DNA lesions characterizes XPF defect with Cockayne syndrome features.Nucleic Acids Res. 2018 Oct 12;46(18):9563-9577. doi: 10.1093/nar/gky774.
• [15] Regulation of Transcription Elongation by the XPG-TFIIH Complex Is Implicated in Cockayne Syndrome.Mol Cell Biol. 2015 Sep;35(18):3178-88. doi: 10.1128/MCB.01401-14. Epub 2015 Jul 6.
• [16] Somatic cell mutation frequency at the HPRT, T-cell antigen receptor and glycophorin A loci in Cockayne syndrome.Mutat Res. 1995 Jul;337(1):49-55. doi: 10.1016/0921-8777(95)00014-b.
• [17] Homozygosity for the WRN Helicase-Inactivating Variant, R834C, does not confer a Werner syndrome clinical phenotype.Sci Rep. 2017 Mar 9;7:44081. doi: 10.1038/srep44081.
• [18] CSB promoter downregulation via histone H3 hypoacetylation is an early determinant of replicative senescence.Nat Commun. 2019 Dec 6;10(1):5576. doi: 10.1038/s41467-019-13314-y.
• [19] Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination.Science. 2018 Dec 7;362(6419):1177-1182. doi: 10.1126/science.aap7607. Epub 2018 Nov 15.
• [20] Ultraviolet-sensitive syndrome cells are defective in transcription-coupled repair of cyclobutane pyrimidine dimers.DNA Repair (Amst). 2002 Aug 6;1(8):629-43. doi: 10.1016/s1568-7864(02)00056-3.
• [21] Analyses of LMNA-negative juvenile progeroid cases confirms biallelic POLR3A mutations in Wiedemann-Rautenstrauch-like syndrome and expands the phenotypic spectrum of PYCR1 mutations.Hum Genet. 2018 Dec;137(11-12):921-939. doi: 10.1007/s00439-018-1957-1. Epub 2018 Nov 19.
• [22] A Transcriptome Study of Progeroid Neurocutaneous Syndrome Reveals POSTN As a New Element in Proline Metabolic Disorder.Aging Dis. 2018 Dec 4;9(6):1043-1057. doi: 10.14336/AD.2018.0222. eCollection 2018 Dec.
• [23] ROS-induced R loops trigger a transcription-coupled but BRCA1/2-independent homologous recombination pathway through CSB.Nat Commun. 2018 Oct 8;9(1):4115. doi: 10.1038/s41467-018-06586-3.
• [24] New Noonan syndrome model mice with RIT1 mutation exhibit cardiac hypertrophy and susceptibility to -adrenergic stimulation-induced cardiac fibrosis.EBioMedicine. 2019 Apr;42:43-53. doi: 10.1016/j.ebiom.2019.03.014. Epub 2019 Mar 18.
• [25] Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndromeassociated Sos1 mutation.J Clin Invest. 2010 Dec;120(12):4353-65. doi: 10.1172/JCI43910.
• [26] Pharmacological Bypass of Cockayne Syndrome B Function in Neuronal Differentiation. Cell Rep. 2016 Mar 22;14(11):2554-61. doi: 10.1016/j.celrep.2016.02.051. Epub 2016 Mar 10.