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. 2018 Jan 25:11:9.
doi: 10.1186/s13039-018-0356-6. eCollection 2018.

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

Zuhair N Al-Hassnan  1   2   3 , Waad Albawardi #  2 , Faten Almutairi #  2 , Rawan AlMass  2 , Albandary AlBakheet  2 , Osama M Mustafa  2 , Laila AlQuait  2 , Zarghuna M A Shinwari  2 , Salma Wakil  2 , Mustafa A Salih  4 , Majid Al-Fayyadh  5 , Saeed M Hassan  4 , Mansour Aljoufan  5 , Osima Al-Nakhli  2 , Brynn Levy  6 , Balsam AlMaarik  2 , Hana A Al-Hakami  2 , Maysoon Alsagob  2 , Dilek Colak  7 , Namik Kaya  2
Affiliations

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

Zuhair N Al-Hassnan et al. Mol Cytogenet. .

Abstract

Background: Quick 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.

Results: Our 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.

Conclusions: This 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.

Keywords: Cervical ankylosis; Congenital heart disease; Fused central vertebrae; Hypoplastic thumb; Osteopenia.

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Conflict of interest statement

The patients were ascertained under Kind Faisal Specialist Hospital and Research Center’s institutionally approved IRB protocols (KFSHRC’s Research Advisory Council Committees including Basic Research Committee and Research Ethics Committee: RAC# 2040042, 2030046, 2120022, 2080032). Before the sample collection, the patients and/or parents (legal guardians) signed the written informed consents.Informed written consents were obtained from the patients. See ethics approval. Copy of the signed consent forms is available upon request.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
The visual diagram is adopted from Chromosome Analysis Suite (Affymetrix Inc.,). From right to left the diagram presents copy number coordinates, the patient’s probe distribution, paternal and maternal probes distributions, OMIM genes, miRNAs, all SNP and copy number probes in the region, and chromosomal coordinates. The patient has 3214 kb deletion (presented in blue color) while father and mother are normal
Fig. 2
Fig. 2
The diagram presents interrogated region, results of the patient’s and parental samples. Copy number status is given next to each tested sample. The patient a duplication comprising more than 50 genes and expanding on approximately 2 Mb region on chromosome 5q35.3. Apparently, parental samples do not carry the gain indicating de novo status of the duplication. The visuals are adopted from Chromosome Analysis Suite (Affymetrix Inc.)
Fig. 3
Fig. 3
Microarray results are displayed for chromosome 2q23.3–24.3 bands. A deletion is seen on 2q24.1 cytoband expanding over more than 249 kb genomic region
Fig. 4
Fig. 4
Microarray result displays for chromosome 16. The second deletion on the patient was observed on chromosome 16q22.2–22.3 bands. The deletion is over 1800 kb detected by more than 1450 molecular markers
Fig. 5
Fig. 5
A deletion on chromosome 2p16.1-p15 is presented in the diagram. The deletion comprises several genes and ~2776 kb genomic region, and detected by 2780 SNP and CN probes
See this image and copyright information in PMC

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