Details of Disease

General Information of Disease (ID: DISBNDZ2)

• Disease Name: Holt-Oram syndrome
• Synonyms: Cardiac-limb syndrome; ventriculo-radial syndrome; heart-hand syndrome, type 1; Hos1; HOS 1; atrio digital syndrome; atrio-digital syndrome; heart-hand syndrome; atriodigital dysplasia; Holt Oram Syndrome; atriodigital dysplasia type 1; heart-hand syndrome type 1; HOLT-Oram syndrome; HOS; Holt-Oram syndrome
• Definition: Holt-Oram syndrome (HOS) is the most common form of heart-hand syndrome and is characterized by skeletal abnormalities of the upper limbs and mild-to-severe congenital cardiac defects.
• Disease Hierarchy:
  DISMT2VZ: Cardiogenetic disease
  DIS5M94B: Non-syndromic limb reduction defect
  DISD0WVL: Multiple congenital anomalies/dysmorphic syndrome without intellectual disability
  DISLNBZJ: Heart-hand syndrome
  DIS3HIWD: Autosomal dominant disease
  DISBNDZ2: Holt-Oram syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0007732
  MESH ID: C535326
  UMLS CUI: C0265264
  OMIM ID: 142900
  MedGen ID: 120524
  Orphanet ID: 392
  SNOMED CT ID: 19092004

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GJA5	TTFQKZ7	Strong	Biomarker	[1]
TGFB2	TTI0KH6	Strong	CausalMutation	[2]

This Disease Is Related to 6 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
KLF13	OTMIKHZ4	Strong	Biomarker	[3]
SMOC1	OTJG2JQY	Strong	Biomarker	[4]
TFAP2B	OTR1T8E9	Strong	Biomarker	[5]
TPR	OTUBBA4W	Strong	Biomarker	[6]
TRIM66	OT0VJCP6	Strong	Biomarker	[7]
TBX5	OT70PISV	Definitive	Autosomal dominant	[8]

References

• [1] Connexin 40, a target of transcription factor Tbx5, patterns wrist, digits, and sternum.Mol Cell Biol. 2005 Jun;25(12):5073-83. doi: 10.1128/MCB.25.12.5073-5083.2005.
• [2] Clinically relevant variants identified in thoracic aortic aneurysm patients by research exome sequencing.Am J Med Genet A. 2016 May;170A(5):1288-94. doi: 10.1002/ajmg.a.37568. Epub 2016 Feb 7.
• [3] KLF13 is a genetic modifier of the Holt-Oram syndrome gene TBX5.Hum Mol Genet. 2017 Mar 1;26(5):942-954. doi: 10.1093/hmg/ddx009.
• [4] SMOC1 is essential for ocular and limb development in humans and mice. Am J Hum Genet. 2011 Jan 7;88(1):30-41. doi: 10.1016/j.ajhg.2010.11.012. Epub 2010 Dec 30.
• [5] A heart-hand syndrome gene: Tfap2b plays a critical role in the development and remodeling of mouse ductus arteriosus and limb patterning.PLoS One. 2011;6(7):e22908. doi: 10.1371/journal.pone.0022908. Epub 2011 Jul 29.
• [6] TPR-MET oncogenic rearrangement: detection by polymerase chain reaction amplification of the transcript and expression in human tumor cell lines.Proc Natl Acad Sci U S A. 1990 Jan;87(2):738-42. doi: 10.1073/pnas.87.2.738.
• [7] TRIM66 overexpresssion contributes to osteosarcoma carcinogenesis and indicates poor survival outcome.Oncotarget. 2015 Sep 15;6(27):23708-19. doi: 10.18632/oncotarget.4291.
• [8] 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.