Unraveling the genetic and developmental mysteries of 22q11 deletion syndrome

Trends Mol Med. 2003 Sep;9(9):383-9. doi: 10.1016/s1471-4914(03)00141-2.


Birth defects occur in nearly 5% of all live births and are the major cause of infant mortality and morbidity. Despite the recent progress in molecular and developmental biology, the underlying genetic etiology of most congenital anomalies remains unknown. Heterozygous deletion of the 22q11.2 locus results in the most common human genetic deletion syndrome, known as DiGeorge syndrome, and has served as an entry to understanding the basis for numerous congenital heart and craniofacial anomalies, among many other defects. Extensive human genetic analyses, mouse modeling and studies of developmental molecular cascades involved in 22q11 deletion syndrome are revealing complex networks of signaling and transcriptional events that are essential for normal embryonic development. Armed with this knowledge, we can now begin to consider the multiple genetic "hits" that might contribute to developmental anomalies, some of which could provide targets for in utero prevention of birth defects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Aorta, Thoracic / abnormalities
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 22 / genetics*
  • DiGeorge Syndrome / congenital
  • DiGeorge Syndrome / embryology*
  • DiGeorge Syndrome / genetics*
  • Humans
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism


  • T-Box Domain Proteins
  • TBX1 protein, human
  • Tbx1 protein, mouse