De novo and complex imbalanced chromosomal rearrangements revealed by array CGH in a patient with an abnormal phenotype and apparently "balanced" paracentric inversion of 14(q21q23).
Karyotypic analysis of a patient exhibiting a phenotype of isolated lissencephaly, and of her parents, revealed a de novo balanced translocation, t(8;17)(p11.2; p13.3). Since the lissencephaly (LIS1) gene was known to be located on 17p13.3, we investigated whether the translocation might involve this gene. We performed Southern analysis using cosmid clones that contained genomic sequences corresponding to LIS1, and found that the breakpoint was located within intron 1. As sequence analysis of the parental chromosomes in the vicinity of the breakpoint identified no additional putative transcripts, haploinsufficiency of the LIS1 gene is likely to be solely responsible for the patient’s lissencephaly. Characterization of both breakpoints indicated a possible involvement of repetitive sequences in the recombigenic process that led to the translocation.