EP_079. Unravelling the mystery of dysmorphism: The role of microarray CGH in detecting submicroscopic chromosomal abnormalities

Azli Ismail^1*, Fadly Ahid², Muhammad Asyraff Mohammed¹, Yuslina Mat Yusoff¹, Zubaidah Zakaria³

1. Hematology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, 40170 Shah Alam, Selangor, Malaysia

2. Centre for Medical Laboratory Technology Studies, Faculty of Health Sciences, Universiti Teknologi MARA, 42300 Puncak Alam, Selangor, Malaysia

3. Premier Integrated Labs, Pantai Hospital Ampang, 55100 Kuala Lumpur, Malaysia

*Corresponding author: Azli Ismail. This email address is being protected from spambots. You need JavaScript enabled to view it.

ABSTRACT

INTRODUCTION: Genome-wide Array Comparative Genomic Hybridization (aCGH) offers high-resolution, rapid microarray analysis, providing information directly linkable to the human genome's physical and genetic maps. This technique simultaneously measures copy number changes at a level of 5-10 kilobases of DNA sequences across multiple loci. This makes aCGH an important tool for studying clinical genetic disorders and developing diagnostic or therapeutic targets. In Malaysia, many patients with syndromic features show normal karyotypes, highlighting the need for a more sensitive method to detect potential chromosomal microaberrations. Current aCGH technology can detect genomic alterations and submicroscopic chromosomal aberrations at multiple loci, which will help explain the cause of these defects.

OBJECTIVE(S): In this study, we will characterise a group of 150 chromosomally-normal patients with unexplained syndromic features using the aCGH method to establish their genotype-phenotype correlation. The locations of the chromosomal breakpoints and the size of the submicroscopic microdeletion and/or microduplication regions in each individual will be identified using the technique.

MATERIALS & METHODS: We selected 150 patients who had previously been determined to be chromosomally normal. Each of these individuals presented with moderate-to-severe mental retardation or developmental delay, in addition to at least one of the following clinical features: facial dysmorphism, microcephaly, or other major abnormalities. To analyze these cases, we performed aCGH using the CytoSure ISCA + SNP array (4x180k) from Oxford Gene Technology, United Kingdom. The results were subsequently analyzed using Cytosure Interpret Software v4.8.32, also from Oxford Gene Technology.

RESULTS: Out of the 150 syndromic patients with unexplained conditions, we identified 73 (49%) individuals with unique microdeletions and/or microduplications on their chromosomes. The sizes of these aberrations ranged from 1.0 to 7.5 Mbp. Importantly, at least 30 genes located within these regions have been previously associated with known clinical genetic syndromes.

CONCLUSION: CGH technology has provided clinical geneticists in our diagnostic laboratory with a powerful new tool for genome-wide screening of syndromic patients. It's now possible to detect many previously unidentified chromosomal changes, which has opened up new avenues for identifying genes involved in disease development. This breakthrough has significant implications for genetic counseling and ultimately, for improving the quality of patient healthcare.

KEYWORDS: Array CGH, Clinical Genetic Syndromes, Dysmorphism