Use of Array Comparative Genomic Hybridization for the Diagnosis of DiGeorge Syndrome in Saudi Arabian Population

Abstract

DiGeorge syndrome (DGS) is a genetic disorder known as a clinically variable syndrome with over 180 associated phenotypic features. It is caused by a common human deletion in the 22q11.2 chromosomal region and currently is affecting approximately 1 in 4,000 individuals. Despite the prevalence of inherited diseases mainly due to consanguineous marriages, the current diagnosis of DGS in Saudi Arabia is mainly based on conventional high-resolution chromosome banding (karyotyping) and FISH techniques. However, advanced genome-wide studies for detecting microdeletions or duplications across the whole genome are needed. The aim of this study is to implement and use aCGH technology in clinical diagnosis of the 22q11.2 deletion in Saudi Arabian DGS patients and to confirm its effectiveness compared to conventional FISH and chromosome banding techniques. Thirty suspected DGS patients were assessed for chromosome 22q11.2 deletion using high-resolution G-banding, FISH, and aCGH. The aCGH results were compared with those obtained by the other 2 cytogenetic techniques. G-banding detected the 22q11.2 deletion in only 1 patient in the cohort. Moreover, it detected additional chromosomal aberrations in 3 other patients. Using FISH, allowed for detection of the 22q11.2 deletion in 2 out of 30 patients. Interestingly, the use of aCGH technique showed deletions in the chromosome 22q11.2 region in 8 patients, indicating a 4-fold increase in diagnostic detection capacity compared to FISH. Our results show the effectiveness of aCGH to overcome the limitations of FISH and G-banding in terms of diagnostic yield and allow whole genome screening and detection of a larger number of deletions and/or duplications in Saudi Arabian DGS patients. Except for balanced translocations and inversions, our data demonstrate the suitability of aCGH in the diagnostics of submicroscopic deletion syndromes such as DGS and most chromosomal aberrations or complex abnormalities scattered throughout the human genome. Our results recommend the implementation of aCGH in clinical genomic testing in Saudi Arabia to improve the diagnostic capabilities of health services while maintaining the use of conventional cytogenetic techniques for subsequent validation or for specific and known aberrations whenever required.

Taiwanese Clinical Experience with Noninvasive Prenatal Testing for DiGeorge Syndrome

“…Seven high-risk cases were regarded as FPs. That is, the current aCGH might not detect all deletions in the critical region [27]. Third, further confirmation of low-risk group was absent due to clinical practice.…”

How Much do we Know About the Findings of 22q11.2 Deletion Syndrome?: A Single-Centre Study with 11-Year Follow-Up

“…The fact that hypocalcemia was not found in the clinical 22q11.2DS patients can be interpreted as this finding does not lead to initial consideration of 22q11.2DS by physicians. Similarly, (14). In another study involving 347 patients, the diagnosis rate by FISH and MLPA analysis was 28.2% (13).…”

Identification of Extremely Rare Pathogenic CNVs by Array CGH in Saudi Children with Developmental Delay, Congenital Malformations, and Intellectual Disability

“…The diagnostic application of array-CGH in Saudi DD/CM/ID patients, to the best of our knowledge, has not been reported yet. However, a few studies have reported the application of array-CGH in the identification of disease-causing variants such as recurrent spontaneous abortion in Saudi Arabia [ 24 ], juvenile myoclonic epilepsy [ 25 ], acute myeloid leukemia [ 26 ], Lynch Syndrome [ 27 ], gastric cancer [ 28 ], Williams’ syndrome [ 29 ], DiGeorge Syndrome [ 30 ], and congenital heart disease [ 31 ]. Hence, in the present study, we aimed to investigate the genetic heterogeneity in Saudi children with DD/CM/ID.…”