Study of Selected X-Linked Disorders: Aicardi Syndrome
| Status: | Recruiting |
|---|---|
| Conditions: | Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 12/6/2018 |
| Start Date: | October 2002 |
| End Date: | January 2020 |
| Contact: | Rajesh Ramakrishnan, PhD |
| Email: | ramakris@bcm.edu |
| Phone: | 832-824-8192 |
Pathogenesis of Selected X-Linked Dominant Disorders and New Strategies to Identify the Gene Mutated in Aicardi Syndrome
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.
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.
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 the participants may be
evaluated by the study collaborators. Blood and skin biopsy will be obtained from affected
individuals, unaffected parents and from other affected or unaffected family members where
indicated. It is anticipated that some severely affected patients will expire; in that case,
(post mortem) pathological specimens may be obtained. Occasionally, affected individuals may
undergo surgical procedures with removal of tissues; in this case we may obtain tissues that
would be otherwise discarded or that are not essential for further diagnostic studies or
clinical care of the patient. It is anticipated that these specimens will be extremely
valuable for understanding the pathogenesis of the investigated conditions. DNA, RNA or
protein will be prepared from leukocytes and from tissues and used for mutation analysis and
other molecular studies of the identified genes. Permanent lymphoblastoid cell lines will be
prepared and stored in the laboratory as a permanent source of DNA for the molecular studies.
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 the participants may be
evaluated by the study collaborators. Blood and skin biopsy will be obtained from affected
individuals, unaffected parents and from other affected or unaffected family members where
indicated. It is anticipated that some severely affected patients will expire; in that case,
(post mortem) pathological specimens may be obtained. Occasionally, affected individuals may
undergo surgical procedures with removal of tissues; in this case we may obtain tissues that
would be otherwise discarded or that are not essential for further diagnostic studies or
clinical care of the patient. It is anticipated that these specimens will be extremely
valuable for understanding the pathogenesis of the investigated conditions. DNA, RNA or
protein will be prepared from leukocytes and from tissues and used for mutation analysis and
other molecular studies of the identified genes. Permanent lymphoblastoid cell lines will be
prepared and stored in the laboratory as a permanent source of DNA for the molecular studies.
Inclusion Criteria:
- Features suggestive of Aicardi syndrome (not all features must be present)
- Agenesis of the corpus callosum
- Chorioretinal lacunae
- Seizures (infantile spasms)
Exclusion Criteria:
We found this trial at
1
site
1200 Moursund Street
Houston, Texas 77030
Houston, Texas 77030
(713) 798-4951
Principal Investigator: Ignatia B Van den Veyver, MD
Phone: 832-824-8125
Baylor College of Medicine Baylor College of Medicine in Houston, the only private medical school...
Click here to add this to my saved trials
