New copy number variants discovered in patients with obesity and intellectual disability

Abstract

Introduction. Intellectual disability (ID) is a neurodevelopment disease characterized by intellectual and adaptive impairment, defined by intelligence quotient (IQ) under 70 and can be affirmed after the age of 6. Until this age, the retard is named development delay (DD). This condition is found in 2-3% of individuals in general population, and 50% of these cases are associated with other clinical features, like pediatric obesity. The genomic study using microarray chromosomal techniques revealed in about 20% of intellectual disability patients a genetic cause of copy number variants (CNVs) type, duplication or deletion, but there is a lack of data about CNVs found in patients with ID/DD associated with obesity. Aim of the study. To find CNVs that could be responsible for the ID/DD associated with obesity phenotype, in 36 Romanian pediatric patients, recruited from the Clinical Emergency Hospital for Children, Cluj-Napoca, Romania. Materials and methods. We used SNP array technique, Infinum OmniExpress 24V1.2 in order to detect CNVs. Data analysis was made using Genome Studio, and the interpretation of the data was performed using UCSC data base (Decipher, ClinVar, Omim and Gene Reviews). Results. We found relevant genetic alterations in 15 patients (42%). Several of them presented deletions and duplications that were described before in international databases, but potential pathogen CNVs not described before were also detected. Therefore, we describe a deletion inside KANSL1, the gene responsive for Koolen-De Vries syndrome, a small deletion in OTC gene, a 8p23.1 duplication in BLK gene and also a patient that presented two uniparental disomies, for chromosome 7 and 13. Conclusions. In this research, we found that 42% of the patients with obesity and intellectual deficiency were carriers of pathogenic genetic abnormalities that can explain their symptoms. Although some of the patients presented classical variants described in literature, some of our findings are variants that were not previously described or were described in very few cases.