Abstracts

To perform mutation screening in candidate genes (EMX2, FLN1, LIS1 and DCX) in a large cohort of patients with different types of cortical malformation. All patients included in this study had CT or high resolution MRI scans. We divided them into three groups according to different stages of cortical development: a) group I: patients with schizencephaly, b) group II: patients with periventricular nodular heterotopia (PNH) and c) group III: patients with the lisencephaly/subcortical band heterotopia spectrum (LIS/SBH). Mutation screening was performed by single strand conformation polymorphism (SSCP), followed by sequencing. We studied 81 patients. Forty seven have schizencephaly, 16 have PNH and 18 have the LIS/SBH spectrum. In 6 patients with schizencephaly we detected SSCP band shifts in the EMX2 gene. We found SSCP band shifts in the FLN1 gene in 7 individuals with PNH. Only one patient with LIS/SBH showed a band shift in the DCX gene; however, 9 of them had band shifts in the LIS1 gene. To date, we have completed the sequencing analysis in 18 of the 23 patients with SSCP band shifts. Normal variants were found in 15 patients, while putative deleterious mutations were detected in only 3 individuals: 2 patients with PNH and mutations in FLN1 and 1 patient with LIS/SBH and mutation in LIS1. Mutation screening in EMX2, FLN1, LIS1 and DCX genes are important to understand pathways involved in cortex development and for genetic counseling. However, most patients with cortical malformations do not have mutations in the candidate genes tested in our study. (Supported by FAPESP.)