Page 15 - Demo

General introduction131Figure 1. Body systems that may be affected in individuals with 22q11.2 microdeletion (McDonaldmcGinn et al.15)22q11.2DS is associated with recurrent hemizygous microdeletions on the long arm (q) of chromosome 22 (Figure 2). Most individuals (90-95%) have a de novo 22q11.2 deletion, meaning that it is not inherited from one of the parents.16 In 85-90% of individuals the deleted region spans from low copy repeat (LCR) A to D. These LCRs are highly similar regions of DNA and susceptible for errors during meiosis.17 The majority of clinical features result from a deletion of the “critical” 22q11.2 region between LCRA-LCRB.18The typically deleted region, LCRA-LCRD, involves ~100 genes of which more than 45 are protein-coding.18 Many genes, that often have multiple functions, have been described to contribute to the 22q11.2DS phenotype including, but not limited to, TBX1, CRKL, DGCR8, PRODH, COMT and (other) genes involved in mitochondrial functioning.18, 19 TBX1 is considered crucial for the 22q11.2DS somatic phenotype, since it is involved in the development of the thymus, thyroid gland, parathyroid glands, cardiac and vascular system.20 CRKL is important for the development of the kidneys and urinary tract, cardiac system, thymus and parathyroid glands, and may act via the same genetic pathways as TBX1.21 COMT encodes for an enzyme