Comprehensive cytogenetic analysis of cases referred for suspected chromosomal abnormalities: A Five-year study at Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, Penang, Malaysia.

Abstract

Chromosomal abnormalities (CA) can affect numerical or structural compositions of chromosomosal DNA leading to a diversity of clinical phenotypic presentations. Awareness of prenatal diagnosis and genetic counselling have improved with advancing medical research but CA remain prevalent as its aetiology is unknown. The objective of this study is to determine the frequencies of various CA in the principle region of north-western Malaysia and compare this data to previous reports to ascertain if statistical differences exist. Karyotype analyses performed at the Genetics Laboratory, Advanced Diagnostic Laboratory (ADL) during the first 5-years of cytogenetic services, totalling 1461 cases, were assessed in this report. Cases suspected of CA were initially diagnosed by clinicians and detailed clinical and family histories were recorded. Peripheral blood lymphocytes of patients were collected and cultured in vitro for acquisition of karyotype by standardized G-banding technique. Fluorescence in situ hybridization (FISH) was conducted in cases suspected of to be DiGeorge, Prader-Willi, Angelman and Williams syndrome. Of the total samples (1805) received and cultured, 1669 (92.46%) successfully yielded results. Abnormal outcomes were observed in 495 cases (29.66%) whereby pronounced majority of cases 299 (68.42%) were Down syndrome. This is followed by Edward, Turner and Patau syndrome, in order of frequency. Numerical CA appears to be prevalent accounting for 85.86% of cases. Structural CA accounted for 14.14% of total positive cases whereby the most common was deletions (34.29%) followed by translocations (20%), ring chromosomes (5.71%), Fragile X syndrome (4.29%), duplications (5.71%) and marker chromosomes (7.14%). The remainder of cases (22.86%) consisted of derivative chromosomes and other complex aberrations. The number of polymorphic variant cases were 27 (1.62%). The number of peripheral blood samples received has significantly increased from 14.3 per month in 2006 to 32.17 per month in 2011. Comparative analysis of our study to previous reports reveal statistical differences in the occurrence of several CA including Edward, Patau, Klinefelter and Fragile-X syndrome. Our experience with peripheral blood samples for cytogenetic analysis demonstrated a success rate of 92.46%. This showed an increase in clinicians validating patients’ diagnoses with karyotyping which is essential in confirming genetic anomalies with the goal to substantiate genetic counselling.