title: Heterogeneity of clinical severity and molecular lesions in Aicardi syndrome.
abstract: All patients with Aicardi syndrome are female or have a 47,XXY karyotype. This finding, along with a report of an Aicardi syndrome patient with an Xp22/autosome translocation, led to the hypothesis that Aicardi syndrome might be caused by an X-linked dominant, male-lethal mutation on the short arm of the X chromosome. To study this hypothesis, we investigated X chromosome inactivation patterns in peripheral lymphocytes from seven patients. We used two methods: methylation-sensitive restriction enzyme analysis and segregation of the active X chromosome in somatic cell hybrids. We found that three of seven cytogenetically normal girls with Aicardi syndrome had profoundly skewed X-inactivation in their lymphocytes, supporting the concept that Aicardi syndrome is X linked. Three of the five girls with the greatest degree of psychomotor retardation and the poorest seizure control had skewed X-inactivation. In contrast, the two highest-functioning children had random X-inactivation. We screened DNA using eight polymorphic probes from the Xp22 region but were unable to identify a deletion in any of the seven patients. Nonrandom X-inactivation in lymphocytes and possibly other tissues in some, but not all, patients with Aicardi syndrome may reflect heterogeneity of their molecular lesions.
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia.
authors.forename: J A
authors.initials: JA
authors.lastname: Neidich
authors.forename: R L
authors.initials: RL
authors.lastname: Nussbaum
authors.forename: R J
authors.initials: RJ
authors.lastname: Packer
authors.forename: B S
authors.initials: BS
authors.lastname: Emanuel
authors.forename: J M
authors.initials: JM
authors.lastname: Puck
mesh_terms: D061085:Agenesis of Corpus Callosum; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D004247:DNA / Q000032:analysis; D015342:DNA Probes; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D013035:Spasm / Q000235:genetics*; D013577:Syndrome; D014960:X Chromosome / Q000032:analysis
chemical_list: D015342:DNA Probes; D004247:DNA