Genetic testing in fetuses with isolated agenesis of the corpus callosum

Purpose: The objectives of this study were to explore genetics pathogenesis of isolated agenesis of corpus callosum (ACC) and assess the utility of chromosomal microarray analysis (CMA) for genetic diagnosis of isolated ACC. Methods: We analyzed the genomes of 16 fetuses with isolated ACC using Afymetrix CytoScan HD arrays and conducted further bioinformatic analysis for one proband fetus with an abnormal copy number variation (CNV). Results: Of the 16 fetal samples examined, two (12.5%) had pathogenic CNVs and three (18.75%) had variants of unknown significance. Two cases, case 2 and case 9, were found to have pathogenic CNVs. Bioinformatic analyses indicated that the CNV of one fetus (case 9) contained 115 annotated coding genes, five of which (SLC6A5, BDNF, ELP4, PAX6, and SLC1A2) have been associated with neurodevelopment. Three of these genes (SLC1A2, BDNF, and PAX6) may play a key role in ACC development. GO cluster analysis of the implicated genes revealed strong representations of protein binding and metal ion binding functions. KEGG pathway analysis pointed to four pathways: longevity regulating pathway, amyotrophic lateral sclerosis, cocaine addiction, and autophagy-animal. Conclusions: BDNF, SLC1A2, and PAX6 may be involved in the development of isolated ACC. CMA is a feasible technology for prenatal diagnosis of isolated ACC.