Most affected individuals have deletions in the 22q ll-qter region from one of their two copies of chromosome 22. These deletions are large, usually spanning at least 2 Mb. In about 20% of cases the deletion is visible when chromosomes are viewed at resolutions of 600 bands or greater. In most cases the deletions are most readily detected by molecular methods, such as commercially available locus-
specific fluorescence in situ hybridization (FISH) probes (Figure 1).
The chromosome 22qll region is particularly rich in duplicated sequences which facilitate recombination and this may be the mechanism which allows for structural mutations such as deletions and duplications. In about 75% of sporadic cases of DGS, the affected chromosome is inherited from the mother. A recent survey found 5% of neonates with congenital heart disease had deletions at 22q.ll. These findings support an extrapolated prevalence of 22qll microdeletions approaching 1:5000. Numerous families have been reported in which deletions passed through several generations causing domi-nantly inherited abnormal phenotypes including DGS.
The mechanism by which the chromosome 22ql 1-qter deletions cause the phenotypic features described below is not established. 'Haploinsuffici-ency' of genes which might be developmentally important in this region is one possibility and DGS has been considered a prototypic 'contiguous gene syndrome' involving an unknown number of genes. Alternatively, the phenotype may result from deletion of a single gene, as is suggested by the recent report of the complete DGS in association with a balanced translocation. A candidate gene disrupted by this translocation has been named HIRA because of homologies with the HIR1 and HIR2 repressors of
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