Role of Pseudogene in Incontinentia Pigmenti, and Its Potential Treatment

Study Overview
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Brief Summary
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Incontinentia Pigmenti (IP) is an X-linked dominant ectodermal dysplastic disorder. It is due to loss of function of NF-Kappa B Essential Modulator (NEMO, inhibitor of Kappa light polypeptide gene enhancer in B cells, Kinase of Gamma, IKBKG), an important regulator of the NF-kB pathway. Major clinical manifestations of IP include swirling skin pigmentary changes, and anomalies in organs including the eyes, dental, bones, nervous system, and heart. Affected male mostly die before birth. Older patients might have immunodeficiency, psychomotor retardation, and seizures. Prenatal diagnosis is difficult. IKBKG gene is 35 kb in length, and contains 10 exons. A pseudogene (∆NEMO, IKBKGP), located distal and in inverse direction to the true gene, contains only exon 3-10. In patients with IP, the most common mutation was exon 4-10 large deletion. But the investigators have found small mutations derived from the pseudogene in Taiwanese patients. The three aims of this study are the role of pseudogene in IP, the frequency of recombination between IKBKG and IKBKGP, and possible treatment. To achieve the first aim, the investigators first develop a pseudogene-specific polymerase chain reaction (PCR). The investigators will first obtain the frequency of IKBKGP gene mutation in normal individuals. The investigators will then detect IKBKGP related mutations in IP patients presenting classical or non-classical symptoms. The latter group of patients, who may have isolated hair, teeth, retinal, or immune problems, are more likely to be caused by point mutations. The second aim of this study is to estimate the incidence of IKBKG and IKBKGP recombination. Because these two genes are in opposite position, recombination after DNA loop back is likely to occur in somatic cells. The investigators will transform lymphocytes containing IKBKGP mutation, and culture them continuously. IKBKG mutation will be check intermittently and the incidence can be estimated. The third aim is to find a treatment. The investigators will test the read-through drug gentamycin and PTC2124 for nonsense mutation. Either fibroblast or Epstein-Barr virus (EBV) - transformed lymphoblasts will be tested. The investigators hope this study with not only increases our understand to IP, and also improves the investigators' knowledge toward genetic diseases.

Official Title
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In Vitro Observation of Chromosome Recombination and Treatment in Vitro

Conditions
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Incontinentia Pigmenti

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed to have Incontinentia Pigmenti Exclusion Criteria: None
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients wiht Incontinentia Pigmenti<br>Patients wiht Incontinentia Pigmenti | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mutation analysis result | Mutation analysis result | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Incontinentia pigmenti, recombination, IKBKG, IKBKGP