Deletion of 17p13 and LIS1 Gene Mutation in Isolated Lissencephaly Sequence

Abstract

Classical lissencephaly is a neuroblast migration disorder that occurs either as isolated lissencephaly sequence or in association with malformation syndromes, such as the Miller-Dieker syndrome. In this work, alterations of the LIS1 gene in patients diagnosed as having isolated lissencephaly sequence were investigated. Ten patients were evaluated for the following aspects: classical cytogenetics by karyotyping using solid staining and G-banding; molecular cytogenetics using fluorescent in situ hybridization with a specific probe for the critical region of isolated lissencephaly sequence; and molecular analysis using deoxyribonucleic acid sequencing. Classical cytogenetic analysis indicated apparently normal karyotypes in all patients, but fluorescent in situ hybridization revealed a 17p13.3 microdeletion in one. In another patient, deoxyribonucleic acid sequencing disclosed a 1 base pair insertion in exon 4 within a sequence of eight consecutive adenine residues (162-163insA), a mutation that predicts a truncated protein. Two different polymorphisms were also detected: a T>C substitution in intron 6 (c.568 + 27bp T>C) and a C>T substitution in the nontranslated region of exon 11 (1250 C>T). These results indicate that cytogenetic analysis and molecular investigation of the LIS1 gene are not always sufficient to determine the disease etiology. These findings are consistent with previous studies and suggest the involvement of other genes in cortical malformation.