Karyotype patterns, clinical features, and parental ages of three predominant live born autosomal trisomies of Northeast Malaysia.

Chromosomal abnormality is one of the causes of congenital disorders among newborns. Despite aneuploidy being the major cause of first trimester miscarriages, very few aneuploidies such as trisomies of chromosomes 13, 18 and 21 survive to birth. The results of 4,064 patients referred for cytogenetic analysis at Human Genome Centre, Universiti Sains Malaysia, Kelantan, Malaysia between 2008 and 2019 were reviewed. We retrospectively investigated the karyotype patterns, clinical features and parental ages of the three common live-born autosomal trisomies such as trisomy 13, trisomy 18 and trisomy 21. The relative frequency of cases with the total sample received and cultured was calculated in each group and compared with those reported elsewhere. Between 2008 and 2019, a total of 1034 live-born trisomic cases which accounted for 25.4% of the 4064 total referred cases and 73.7% of 1403 suspected trisomy cases, were identified, with age ranging from newborns to 57 years. Down syndrome was the commonest aneuploidy (857 cases; 21.1%) followed by Edwards syndrome (133 cases; 3.3%) and Patau syndrome (44 cases; 1.1%). The number of diagnosed cases for each of the trisomies was fairly stable from year to year. About two-thirds of both maternal and paternal ages were ≥ 35 years. This is the first cytogenetic report on the common live-born autosomal trisomies in the North-Eastern region of Malaysia. The prevalence of trisomies 21 was found to be higher compared to an earlier study in the North-Western region of Malaysia, wherein also, advanced maternal age was a significant risk factor.

Clinical implications of conventional cytogenetics, fluorescence in situ hybridization (FISH) and molecular testing in chronic myeloid leukaemia patients in the tyrosine kinase inhibitor era - A review.

Chronic myeloid leukaemia (CML) provides an illustrative disease model for both molecular pathogenesis of cancer and rational drug therapy. Imatinib mesylate (IM), a BCR-ABL1 targeted tyrosine kinase inhibitor (TKI) drug, is the first line gold standard drug for CML treatment. Conventional cytogenetic analysis (CCA) can identify the standard and variant Philadelphia (Ph) chromosome, and any additional complex chromosome abnormalities at diagnosis as well as during treatment course. Fluorescence in situ hybridization (FISH) is especially important for cells of CML patients with inadequate or inferior quality metaphases or those with variant Ph translocations. CCA in conjunction with FISH can serve as powerful tools in all phases of CML including the diagnosis, prognosis, risk stratification and monitoring of cytogenetic responses to treatment. Molecular techniques such as reverse transcriptase-polymerase chain reaction (RT-PCR) is used for the detection of BCR-ABL1 transcripts at diagnosis whereas quantitative reverse transcriptase-polymerase chain reaction (qRTPCR) is used at the time of diagnosis as well as during TKI therapy for the quantitation of BCR-ABL1 transcripts to evaluate the molecular response and minimal residual disease (MRD). Despite the excellent treatment results obtained after the introduction of TKI drugs, especially Imatinib mesylate (IM), resistance to TKIs develops in approximately 35% - 40% of CML patients on TKI therapy. Since point mutations in BCR-ABL1 are a common cause of IM resistance, mutation analysis is important in IM resistant patients. Mutations are reliably detected by nested PCR amplification of the translocated ABL1 kinase domain followed by direct sequencing of the entire amplified kinase domain. The objective of this review is to highlight the importance of regular and timely CCA, FISH analysis and molecular testing in the diagnosis, prognosis, assessment of therapeutic efficacy, evaluation of MRD and in the detection of BCR-ABL1 kinase mutations which cause therapeutic resistance in adult CML patients.