Clinical and genetic characteristics of patients with idiopathic intellectual disability and chromosomal microduplications

Introduction: Copy number variation is regarded as one of the leading genetic causes of intellectual disorders. About 230 microdeletions and only about 80 microduplication syndromes are described in patients with intellectual disability and developmental disorders. In connection with the prevalence of microdeletions with proven pathogenetic significance, the question arises about underestimation of the role of microduplications in the realization of pathological conditions. Aim: search for pathogenetically significant chromosomal microduplications in patients with idiopathic intellectual disability and characterization of their clinical manifestations. Materials and Methods: Using 8х60K arrays the molecular karyotyping for 200 children of 2-18 years old with developmental delay, intellectual disability (IQ 50-70), and dysmorphic features / congenital anomalies was performed. Verification and analysis of the origin of microduplications were carried out using PCR-RT. Results: Seventy patients (35%) showed no clinical significant CNV, and 63 (31.5%) reported benign variants. A wide spectrum of pathogenic and potentially pathogenic CNVs was identified for 67 patients (33.5%), not detected with standard karyotyping. In 39 children of CNVs with probable pathogenetic significance, 14 deletions and 25 duplications were identified, which in the general group of patients consist of 7% and 12.5%, respectively. Eighteen patients (9%) had combinations of different types of CNVs (with pathogenic and potentially pathogenic significance). Ten patients (5%) were diagnosed with a microdeletion / microduplication syndrome. Conclusions: We determined the frequency, spectrum, origin of clinically significant chromosomal microduplications in patients with idiopathic intellectual disability and characterized its clinical manifestations. Timely molecular cytogenetic diagnosis is important for elucidating the causes of the disease and providing quality medical genetic counseling for the family.

недифференцированные интеллектуальные нарушения, матричная сравнительная геномная гибридизация, хромосомные микродупликации. Авторы сообщают об отсутствии конфликта интересов, undifferentiated intellectual disability, array comparative genomic hybridization, chromosomal microduplications

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