USING OF MULTIPLE CHROMOSOMAL AND MOLECULAR ANALYSES TO ELUCIDATE THE ETIOLOGY OF PLURIMALFORMATIVE SYNDROMES
Abstract
Congenital anomalies are structural or functional abnormalities occurring during intrauterine life in 3% of all pregnancies, representing an important public health problem through frequency, morbidity and mortality. In 6% of cases they are determined by unbalanced chromosomal abnormalities and their cytogenetic diagnosis is a prerequisite for proper management including proper genetic counseling. Material and methods: The retrospective study included 331 patients who were investigated by clinical and cytogenetic (conventional or molecular) methods at the Genetics Pathology Center in Iaşi, from 1 January 2015 to 31 December 2016. Results: The study group was divided into four subgroups: patients with plurimalformative syndromes or patients with association of multiple congenital anomalies (108 cases of which in 25 patients were confirmed with an unbalanced structural or numerical chromosomal abnormalities), patients with craniofacial dysmorphism (88 cases - in five cases cytogenetic abnormalities were confirmed), patients with Down syndrome (96 cases - 90 being cytogenetically confirmed), patients with Turner syndrome (39 cases of which 16 were cytogenetically confirmed). In 24 patients Fluorescence in Situ Hybridization (FISH) was applied with probes for the chromosomal regions involved in clinically suspected microdeletion syndromes and in 12 cases these were confirmed. In the other 12 cases (not confirmed by karyotype / FISH) we demonstrated that the syndrome is generated by another type of molecular mechanism using Multiplex ligation dependent probes amplification (MLPA). In 11 cases with complex chromosomal abnormalities, the investigation continued and the array CGH investigation is still in progress. Conclusions: Elucidation of the chromosomal etiology of congenital anomalies is important for providing appropriate genetic counseling and identifying other people with high genetic risk in their family.
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