Page 15 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

General introduction
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Figure 1. Body systems that may be affected in individuals with 22q11.2 microdeletion (McDonald-
mcGinn 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.18
The 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
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