Clinical Trial: Study of Selected X-Linked Disorders: Aicardi Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Pathogenesis of Selected X-Linked Dominant Disorders and New Strategies to Identify the Gene Mutated in Aicardi Syndrome

Brief Summary: Based on our current understanding of Aicardi syndrome, the condition is hypothesized to occur due to a genetic change on the X-chromosome. Our team is investigating Aicardi syndrome to identify the specific gene location associated with the disorder. We are collecting blood and skin biopsy samples from patients and their parents. A permanent cell line is prepared and DNA from the blood and skin samples and cell lines is isolated and then used for genetic testing. Our current research includes microarray analysis which we are using to look for duplications or deletions of genetic material, mutation analysis of candidate genes by sequencing, review of medical records to identify trends suggesting possible candidate genes of interest, and X chromosome inactivation studies.

Detailed Summary:

Aicardi syndrome is a sporadic X-linked dominant, presumably male-lethal, neurodevelopmental disorder. It was initially characterized by agenesis of the corpus callosum, neuronal migration defects, eye abnormalities (chorioretinal lacunae, colobomas of the optic nerve and microphthalmia) and severe early-onset seizures and neurodevelopmental delay. It is now well recognized that other brain abnormalities, such as polymicrogyria, agyria, cysts and heterotopias are common features of Aicardi syndrome. We previously hypothesized that the gene causing Aicardi syndrome and possibly additional phenotypically similar disorders with X-linked inheritance, such as Goltz syndrome or Focal Dermal Hypoplasia, are in or near the region on chromosome Xp22 that is deleted in another condition named microphthalmia with linear skin defects syndrome (MLS), because all three have some clinical similarities. However, interim studies have shown that this is likely not the case because no mutations were found in Aicardi syndrome in human holocytochrome c-type synthetase (HCCS) , the gene that is deleted or mutated in MLS. In addition, a mouse model for MLS has no features of Aicardi syndrome. Furthermore, we identified mutations in PORCN (Xp11.3) in Goltz syndrome patients, but not in Aicardi syndrome patients. Therefore, it is likely that the mutated gene is elsewhere on the X-chromosome.

For this study we are collecting information on patients with clinical findings suggesting a diagnosis of Aicardi syndrome, MLS syndrome or a condition that phenotypically overlaps with these disorders. A detailed family history will be obtained, when indicated, and additional family members will be evaluated after appropriately obtained written voluntary consent. A detailed report of the history or physical findings will be obtained from referring physicians for patients identified at outside facilities, or
Sponsor: Baylor College of Medicine

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Information By: Baylor College of Medicine

Dates:
Date Received: June 11, 2008
Date Started: October 2002
Date Completion: January 2020
Last Updated: May 4, 2017
Last Verified: May 2017