A genome-wide screen for copy number alterations in Aicardi syndrome.

Aicardi syndrome is a severe neurodevelopmental disorder that affects females or rarely males with a 47,XXY karyotype. Therefore, it is thought to be caused by heterozygous defects in an essential X-linked gene or by defects in an autosomal gene with sex-limited expression. Because all reported cases are sporadic with one exception, traditional linkage analysis to identify the mutant gene is not possible, and the de novo mutation rate must be high. As an alternative approach to localize the mutant gene, we screened the DNA of 38 girls with Aicardi syndrome by high-resolution, genome-wide array comparative genomic hybridization for copy number gains and losses. We found 110 copy number variants (CNVs), 97 of which are known, presumably polymorphic, CNVs; 8 have been seen before in unrelated studies in unaffected individuals. Four previously unseen CNVs on autosomes were each inherited from a healthy parent. One subject with Aicardi syndrome had a de novo loss of X-linked copy number in a region without known genes. Detailed analysis of this and flanking regions did not reveal CNVs or mutations in annotated genes in other affected subjects. We conclude that, in this study population of 38 subjects, Aicardi syndrome is not caused by CNVs detectable with the high-resolution array platform that was used.