A Novel 22q11.2 Microdeletion in DiGeorge Syndrome

The recurrent distal 22q11.2 microdeletions are often de novo and do not represent a single clinical entity: a proposed categorization system

“…DD and/or ID have been reported in more than 80% of distal 22q11.2 microdeletion patients described in the literature to date and tend to be relatively mild to moderate in severity. [7][8][9][10][11][12][13][14][15][16][17][18] Taken together, global DD and ID seem to be key components of the distal 22q11.2 microdeletions phenotype irrespective of the size and position of the deletion. Behavioral and neurological problems were also quite common in our patients in all deletion types.…”

“…[7][8][9][10][11][12][13][14][15][16][17][18] These deletions are mediated by nonallelic homologous recombination between the five telomeric LCR22s (LCR22-D to -H) in the distal portion of the 22q11.2 region (Figure 2). 10 Distal 22q11.2 microdeletions that span the LCR22-F to -G interval encompassing the tumor suppressor SMARCB1 gene (also called INI1) have been reported to manifest many of the presenting features mentioned above but also have high incidence of malignant rhabdoid tumors in infancy and early childhood, predominantly in the kidneys and central nervous system, which necessitates tumor surveillance in these patients.…”

“…[7][8][9][10][11][12][13][14][15][16][17][18] Moreover, some patients present with cleft lip and/or cleft palate. Although some of our patients manifested some of these features, the majority of them presented with nonspecific, nondiagnostic features that were quite variable, as shown in the Results section.…”

“…6 Recently, others and we demonstrated that the five telomeric LCR22s, namely LCR22-D to H, at the distal portion of 22q11.2 are causally implicated in the recurrent distal 22q11.2 microdeletion-associated phenotype(s) (OMIM 611867), and their reciprocal microduplications in the region immediately distal to the DG/VCFs typically deleted region (Figure 2). [7][8][9][10][11][12][13][14][15][16][17][18] The structure of the LCR22-D, -E, and -F has been studied and was shown to contain the BCRL module in each LCR22, suggesting that the distal 22q11.2 microdeletions/microduplications are mediated by nonallelic homologous recombination. 10 To date, the distal 22q11.2 microdeletions have been grouped together as a single clinical entity despite the fact that these deletions are variable in size and position depending on the Purpose: The five segmental duplications (LCR22-D to -H) at the distal region of chromosome 22 band q11.2 in the region immediately distal to the DiGeorge/velocardiofacial syndrome deleted region have been implicated in the recurrent distal 22q11.2 microdeletions.…”

Atypical deletions suggest five 22q11.2 critical regions related to the DiGeorge/velo-cardio-facial syndrome

“…5 However, a number of patients with non-overlapping deletions and similar phenotype excludes this model as the pathogenic mechanism. [6][7][8][9] Molecular studies have defined at least four minimum critical regions, the deletion of which results in the DGS/VCFS phenotype. 8,9 The first small region of overlap (SRO1), about 300 Kb in size, was defined by molecular analysis of patients carrying rare rearrangements, including the translocation between chromosomes 2 and 22 (ADU), associated either with DGS or VCFS phenotypes.…”