Varijacije u broju kopija na hromozomu 15 detektovane molekularnom kariotipizacijom kod pacijenata sa razvojnim kašnjenjem i urođenim anomalijama

Abstract

Introduction: Global developmental delay (GDD) and congenital anomalies represent a heterogeneous group of medical conditions that may have a known genetic etiology. Molecular karyotyping is the gold standard for detecting copy number variations (CNV), and the first-line test in patients with GDD and congenital anomalies, with an average diagnostic yield of 15%. Chromosome 15 (C15) is one of the chromosomes on which CNV occurs most frequently. Aim: To analyze all detected (significant) CNVs on C15 in patients with GKR and/or congenital anomalies, estimate their share in the overall CNV detection rate of different pathogenicity classes, and present several illustrative cases. Material and methods: In the total sample of 350 patients analyzed by molecular karyotyping technique, 92 with detected significant CNV were singled out. All patients with variants on C15 were then analyzed and further classified according to type, size, and clinical significance. Results: In 11 patients, at least one significant CNV was detected on chromosome 15, which is 3.15% of the total sample and 11.96% of a sample of patients with significant CNV of any localization. In 72.7% cases, CNV was described as pathogenic or likely pathogenic and in 27.3% as a variant of unknown significance. In the total detection rate of csCNV from all chromosomes 15.4%, the percentage of variations from C15 was 17.2%. Conclusion: The detection rate of csCNVs on C15 in the diagnostic yield of the molecular karyotypisation of patients with GDD and congenital anomalies is 17.2%, which confirms that they make up a significant portion of the GDD etiology.