Details of Disease

General Information of Disease (ID: DISGVBCV)

• Disease Name: Rothmund-Thomson syndrome
• Synonyms: poikiloderma congenitale; poikiloderma atrophicans and cataract; RTS; Rothmund-Thomson syndrome; poikiloderma of Rothmund-Thomson; congenital poikiloderma
• Definition: Rothmund-Thomson syndrome (RTS) is a genodermatosis presenting with a characteristic facial rash (poikiloderma) associated with short stature due to pre- and postnatal growth delay, sparse scalp hair, sparse or absent eyelashes and/or eyebrows, juvenile cataracts, skeletal abnormalities, radial ray defects, premature aging and a predisposition to certain cancers.|Editor note: check whether properties apply to both 1 and 2, or just type 2
• Disease Hierarchy:
  DISQCXZX: Disorder of development or morphogenesis
  DISLXQHV: Telomere syndrome
  DISGXLG5: Hereditary neoplastic syndrome
  DISYJQB2: Hereditary photodermatosis
  DISGVBCV: Rothmund-Thomson syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0010002
  MESH ID: D011038
  UMLS CUI: C0032339
  MedGen ID: 10819
  Orphanet ID: 2909
  SNOMED CT ID: 69093006

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
EIF4E	TTZGCP6	Limited	Biomarker	[1]
TMPRSS11D	TTWHYC8	Limited	Altered Expression	[2]
HDAC8	TTT6LFV	moderate	Genetic Variation	[3]
CREBBP	TTFRCTK	Strong	Genetic Variation	[4]
WRN	TT2H5WQ	Strong	Genetic Variation	[5]

This Disease Is Related to 13 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
OPN1LW	OTFNUZ7O	Limited	Biomarker	[1]
PAG1	OTFOJUIQ	Limited	Biomarker	[1]
PCBP4	OTDLL4NB	Limited	Biomarker	[1]
BLM	OTEJOAJX	Strong	Biomarker	[6]
CDC45	OT6NNLOD	Strong	Biomarker	[7]
DRC1	OT7WLL0X	Strong	Biomarker	[7]
ENOSF1	OT65D3ZK	Strong	Genetic Variation	[8]
FAM111B	OT9IQ9NV	Strong	Biomarker	[9]
GINS4	OTCVOO3S	Strong	Biomarker	[7]
HFM1	OTHV3EFE	Strong	Genetic Variation	[10]
RECQL	OTPCH3JH	Strong	Genetic Variation	[11]
SLURP1	OT89YD2E	Strong	Biomarker	[12]
RECQL4	OT59LSW7	Definitive	Autosomal recessive	[13]

References

• [1] Mutation of the CH1 Domain in the Histone Acetyltransferase CREBBP Results in Autism-Relevant Behaviors in Mice.PLoS One. 2016 Jan 5;11(1):e0146366. doi: 10.1371/journal.pone.0146366. eCollection 2016.
• [2] Loss of CBP acetyltransferase activity by PHD finger mutations in Rubinstein-Taybi syndrome.Hum Mol Genet. 2003 Feb 15;12(4):441-50. doi: 10.1093/hmg/ddg039.
• [3] Exome sequencing identifies a novel EP300 frame shift mutation in a patient with features that overlap Cornelia de Lange syndrome.Am J Med Genet A. 2014 Jan;164A(1):251-8. doi: 10.1002/ajmg.a.36237. Epub 2013 Oct 29.
• [4] Genotype-phenotype specificity in Menke-Hennekam syndrome caused by missense variants in exon 30 or 31 of CREBBP.Am J Med Genet A. 2019 Jun;179(6):1058-1062. doi: 10.1002/ajmg.a.61131. Epub 2019 Mar 20.
• [5] Functional conservation of RecQ helicase BLM between humans and Drosophila melanogaster.Sci Rep. 2019 Nov 26;9(1):17527. doi: 10.1038/s41598-019-54101-5.
• [6] RECQL4, the protein mutated in Rothmund-Thomson syndrome, functions in telomere maintenance.J Biol Chem. 2012 Jan 2;287(1):196-209. doi: 10.1074/jbc.M111.295063. Epub 2011 Oct 28.
• [7] Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome.Cell. 2005 Jun 17;121(6):887-98. doi: 10.1016/j.cell.2005.05.015.
• [8] Targeted next-generation sequencing appoints c16orf57 as clericuzio-type poikiloderma with neutropenia gene. Am J Hum Genet. 2010 Jan;86(1):72-6. doi: 10.1016/j.ajhg.2009.11.014. Epub 2009 Dec 10.
• [9] Mutations in FAM111B cause hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis. Am J Hum Genet. 2013 Dec 5;93(6):1100-7. doi: 10.1016/j.ajhg.2013.10.013. Epub 2013 Nov 21.
• [10] Rothmund-Thomson syndrome.Orphanet J Rare Dis. 2010 Jan 29;5:2. doi: 10.1186/1750-1172-5-2.
• [11] Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases. Hum Mol Genet. 2003 Nov 1;12(21):2837-44. doi: 10.1093/hmg/ddg306. Epub 2003 Sep 2.
• [12] Palmoplantar keratoderma along with neuromuscular and metabolic phenotypes in Slurp1-deficient mice.J Invest Dermatol. 2014 Jun;134(6):1589-1598. doi: 10.1038/jid.2014.19. Epub 2014 Jan 17.
• [13] 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.