Different Types of Deletions Created by Low-Copy Repeats Sequences Location in 22q11.2 Deletion Syndrome:...

The most frequent microdeletion, 22q11.2 deletion syndrome (22q11.2DS), has a wide and variable phenotype that causes difficulties in diagnosis. 22q11.2DS is a contiguous gene syndrome, but due to the existence of several low-copy-number repeat sequences (LCR) it displays a high variety of deletion types: typical deletions LCR A-D-the most common (~90%), proximal deletions LCR A-B, central deletions (LCR B, C-D) and distal deletions (LCR D-E, F).

We conducted a retrospective study of 59 22q11.2SD cases, with the aim of highlighting phenotype-genotype correlations. All cases were tested using MLPA combined kits: SALSA MLPA KIT P245 and P250 (MRC Holland).

most cases (76%) presented classic deletion LCR A-D with various severity and phenotypic findings. A total of 14 atypical new deletions were identified: 2 proximal deletions LCR A-B, 1 CES (Cat Eye Syndrome region) to LCR B deletion, 4 nested deletions LCR B-D and 1 LCR C-D, 3 LCR A-E deletions, 1 LCR D-E, and 2 small single gene deletions: delDGCR8 and delTOP3B.

This study emphasizes the wide phenotypic variety and incomplete penetrance of 22q11.2DS. Our findings contribute to the genotype-phenotype data regarding different types of 22q11.2 deletions and illustrate the usefulness of MLPA combined kits in 22q11.2DS diagnosis.