Analysing results and clinical features of cases referred for microarray testing in a single center with literature review

Cognitive impairment and/or congenital anomalies, despite being rare in the population, represent a disease group with a broad etiological spectrum. Structural chromosomal anomalies are among the significant causes that lead to clinical findings such as learning difficulties, dysmorphic facial features, various congenital anomalies, growth and developmental delays. Only anomalies larger than 5 Mb can be detected using conventional cytogenetic methods. Microarray testing allows for the detection of small deletions and duplications located in interstitial regions. Today, with the help of array-based methods, (array CGH, SNP array, etc.), diagnoses can be made for 15-20% of this patient group. In this study, we retrospectively evaluated the analysis results and clinical features of a total of 51 cases referred to a single center for microarray testing, with literature review. SNP array data were obtained using the Illumina Infinium Global Screening Array platform. According to the analysis results, a significant portion of the patients had pathogenic and likely pathogenic copy number variations (CNVs). Some of these variations had been previously reported in the literature and were assessed as genetic changes consistent with clinical findings. In addition, some new and previously unreported CNVs were identified, adding valuable information to the existing literature. The findings reaffirm that SNP array testing is a crucial tool in the diagnosis and management of genetic disorders. In our study, the unique breakpoints in each patient emphasized the importance of evaluating the genes within the altered regions for haploinsufficiency/triplosensitivity. This also highlighted the necessity of expanding working groups like ClinGen, which curate gene/genomic regions. Additionally, during microarray testing analysis, the importance of evidence-based scoring of the characteristics of CNVs (number and content of genes, literature data, family segregation etc.) was underscored. In conclusion, correlating SNP array results with clinical features facilitates a better understanding of diseases and enables accurate genetic counseling for patients. We believe that larger-scale cohort and case-control studies, along with an increase in global working groups involved in the curation of CNVs, will more clearly demonstrate the clinical benefits of SNP array testing in the future. Keywords: Copy number variation, microarray analysis, SNP array, cognitive impairment