Identification of novel genomic imbalances in Saudi patients with congenital heart disease

Abstract

BackgroundQuick genetic diagnosis of a patient with congenital heart disease (CHD) is quite important for proper health care and management. Copy number variations (CNV), chromosomal imbalances and rearrangements have been frequently associated with CHD. Previously, due to limitations of microscope based standard karyotyping techniques copious CNVs and submicroscopic imbalances could not be detected in numerous CHD patients. The aim of our study is to identify cytogenetic abnormalities among the selected CHD cases (n = 17) of the cohort using high density oligo arrays.ResultsOur screening study indicated that six patients (~35%) have various cytogenetic abnormalities. Among the patients, only patient 2 had a duplication whereas the rest carried various deletions. The patients 1, 4 and 6 have only single large deletions throughout their genome; a 3.2 Mb deletion on chromosome 7, a 3.35 Mb deletion on chromosome 3, and a 2.78 Mb a deletion on chromosome 2, respectively. Patients 3 and 5 have two deletions on different chromosomes. Patient 3 has deletions on chromosome 2 (2q24.1; 249 kb) and 16 (16q22.2; 1.8 Mb). Patient 4 has a 3.35 Mb an interstitial deletion on chromosome 3 (3q13.2q13.31).Based on our search on the latest available literature, our study is the first inclusive array CGH evaluation on Saudi cohort of CHD patients.ConclusionsThis study emphasizes the importance of the arrays in genetic diagnosis of CHD. Based on our results the high resolution arrays should be utilized as first-tier diagnostic tool in clinical care as suggested before by others. Moreover, previously evaluated negative CHD cases (based on standard karyotyping methods) should be re-examined by microarray based cytogenetic methods.

Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways

“…CMA and karyotyping are the two screening methods which can supplement each other, and thus, negative karyotyping results should be re-examined by using chromosomal microarrays [165]. Studies have associated the occurrence of copy number variants and congenital heart diseases [166,167] and other malformations such as that of limbs [168].…”

Consanguineous Marriage and Its Association With Genetic Disorders in Saudi Arabia: A Review

“…Al-Hassnan et al conducted a comprehensive array of CGH studies on a Saudi cohort with CHD [ 60 ]. They identified cytogenetic imbalances in 17 CHD cases with additional conditions like autism spectrum disorder, intellectual disability, and developmental delays.…”

“…They identified cytogenetic imbalances in 17 CHD cases with additional conditions like autism spectrum disorder, intellectual disability, and developmental delays. Notably, a chromosomal deletion on 12p12.1 involving SOX5 was found in a child of consanguineous parents [ 60 ]. This supports previous findings linking SOX5 haploinsufficiency to various CHD anomalies [ 61 ].…”