The Identification of Microdeletion and Reciprocal Microduplication in 22q11.2 Using High-Resolution CMA Technology

Abstract

The chromosome 22q11.2 region has long been implicated in genomic diseases. Some genomic regions exhibit numerous low copy repeats with high identity in which they provide increased genomic instability and mediate deletions and duplications in many disorders. DiGeorge Syndrome is the most common deletion syndrome and reciprocal duplications could be occurring in half of the frequency of microdeletions. We described five patients with phenotypic variability that carries deletions or reciprocal duplications at 22q11.2 detected by Chromosomal Microarray Analysis. The CytoScan HD technology was used to detect changes in the genome copy number variation of patients who had clinical indication to global developmental delay and a normal karyotype. We observed in our study three microdeletions and two microduplications in 22q11.2 region with variable intervals containing known genes and unstudied transcripts as well as the LCRs that are often flanking and within this genomic rearrangement. The identification of these variants is of particular interest because it may provide insight into genes or genomic regions that are crucial for specific phenotypic manifestations and are useful to assist in the quest for understanding the mechanisms subjacent to genomic deletions and duplications.

Navigating diagnostic options for inborn errors of immunity in children: a case-based illustration

“…22q11.2 deletion is the second most common cause of congenital heart disease and developmental delays, and the most common cause of syndromic palatal anomalies [15]. The chromosome 22q11.2 region contains eight low copy repeats, which are known to lead to increased genomic instability and mediate deletions and duplications [21]. Current microarray technology has increased our ability to detect these copy number variations and aid in the diagnosis of patients with multiple congenital anomalies [22].…”

Genotypic and phenotypic variability of 22q11.2 microdeletions – an institutional experience

“…22q11.2 deletion syndrome was traditionally detected as megabase (mb) deletions including TBX1 gene in the region resulting in syndromic features of DGS and VCFS. However, an increasing number of studies using chromosome microarray (CMA) have reported a significant number of symptomatic patients harboring smaller 22q11.2 microdeletions, with some as small as 100 kilobase (kb), with or without TBX1 gene [ 1 , 3 , 4 , 7 ]. Moreover, several studies involving DGS/VCFS patients diagnosed before genetic testing was widely available have reported an increasing variation of phenotypes, including non-classic phenotypes such as genitourinary abnormalities, prematurity, and skeletal defects [ 1 , 8 – 11 ].…”