Cytogenetic and Molecular Cytogenetics (FISH) Study amang Sudanes Patients with Constitutional Chromosomal Changes and Microdeletion Syndromes

Abstract

ABSTRACT Objectives: To evaluate the chromosomal changes in Sudanese patients with suspected chromosomal abnormality referred for cytogenetic analysis. Material and Methods: A total of 1500 patients referred during 2009 and 2013 for cytogenetic to Cytogenetic Unit at Al Neelian medical research center, faculty of medicine, Al Neelian University, Sudan. The patients had various presentation including mental retardation, multiple congenital malformations, dysmorphic feature, primary and secondary amenorrhea, ambiguous genitaliaو and recurrent miscarriage. Conventional Cytogenetic analyses performed in peripheral blood samples that cultured in RPMI 1640 medium for three days. microdeletion not detected by conventional light microscopy were submitted to the fluorescence In situ hybridization (FISH) technique, FISH technique was done according to modification of Pinkle, The clonality criteria and the karyotype descriptions were according to the international system for Human Cytogenetic Nomenclature recommendations (ISCN). 2009 recommendations Results: Of the 1500 patients investigated, 330 (22%) patients showed abnormal karyotypes and 1170 (78%) showed normal karyotypic findings. Out of the 330 patients with abnormal karyotypes, 310 (94%) patients showed numerical abnormalities whereas 20 (6%) patients revealed structural abnormalities. The most common karyotypic abnormalities were Down's syndrome seen in 230 (74.1%) patients. Abnormalities, of sex chromosome seen in 69 (20.9%) of all patients of which 52 showed karyotype consistent with turner's syndrome ( 16.7%), Nine patients 2.6% consistent with Klinefelter‘s syndrome, 3 patients 0.9% consistent with XXX, developmental of sexual diseases seen in 5 patients (1.6%). 8 patients (2.4%), consistent with Edwards's syndromes. Patau's syndromes were observed in two patients (0.6%). Abnormalities of Other chromosome were seen in seven patients (1.6%). 2 Structure abnormalities found in 20 patients,(79.2%) of them present with menatal retardation, deletion consistent in 3 patients (15%) inversion consistent in 2 patients (10%) translocation consistent in 11 patients (55%), fragile X consistent in 3 patients (15%), Derivative in one patient (5%). FISH technique was done for 17 cases that suspected of micro deletion syndrome of which, 9 patients, (52.9%) showed abnormality consistent with diagnosis of DiGeorge syndrome in 3 patients, Angelman syndrome in 2 patients, and Prader-Willi Syndrome in the remaining 4 patients. Conclusions: The present study, the first ever in Sudan, showed high incidence of chromosomal abnormalities (22%). This justifies the needs for cytogenetic analysis in patients with clinical suspicions. Cytogenetic tests are complicated, time consuming and expensive. Most laboratories can handle only a limited number of specimens and thus physician should request the cytogenetic test in cases with justified indication. The frequency of microdeletion detected (52.9%) in cases with normal initial karyotype justify the use of FISH analysis as complimentary test in microdeletion suspicious cases. Moreover, a multi-disciplinary strategy is needed to aid in clinical management and counseling.