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22q11 Deletion Syndrome: A Role for Tbx1 in Pharynx and Cardiovascular Development

  1. Amelie Calmont,
  2. Peter Scambler

Published Online: 15 SEP 2010

DOI: 10.1002/9780470015902.a0006074.pub2



How to Cite

Calmont, A. and Scambler, P. 2010. 22q11 Deletion Syndrome: A Role for Tbx1 in Pharynx and Cardiovascular Development. eLS. .

Author Information

  1. Institute of Child Health, Molecular Medicine Unit, London, UK

Publication History

  1. Published Online: 15 SEP 2010


DiGeorge and velocardiofacial syndromes result from a chromosomal deletion involving proximal chromosome 22 and affected individuals commonly present with congenital heart defects, feeding problems, speech delay and learning problems. Psychiatric illness may present later in life. Mutation analysis and creation of mouse models which mimic the human disorder have identified that the Tbx1 (T-box 1) transcription factor is the major dosage-sensitive gene in the deletion region and have allowed exploration of the underlying developmental pathways and signalling networks disrupted in these syndromes. Of particular importance in this regard are Fgf (fibroblast growth factor) and retinoic acid signalling. Tbx1 is in genetic epistasis with loci encoding several transcription factors and signalling molecules, providing some rationale for the very variable clinical presentation. Gain-of-function, or duplications containing Tbx1, is also associated with heart defect.

Key Concepts:

  • The presence of a dominant phenotype secondary to gene hemizygosity is called haploinsufficiency.

  • Genetic epistasis is the phenomenon where the effects of one gene are modified by one or several other genes, which are called modifier genes.

  • Each pharyngeal arch surrounds an arch artery that connects the heart, by means of the aortic sac, to the dorsal aortae.

  • The neural crest is a pluripotent embryonic neuroectodermal cell population that migrates extensively and differentiates into diverse structures such as the face, neck, heart, adrenal gland, peripheral nervous system and skin.

  • Low copy number repeat are 1–400 kb blocks of genomic sequence that are duplicated in one or more locations on a chromosome and can act as substrates for aberrant recombination events.


  • Tbx1;
  • DiGeorge syndrome;
  • velocardiofacial syndrome;
  • conotruncal anomaly face syndrome