Role of Pseudogene in Incontinentia Pigmenti, and Its Potential Treatment

This study has been completed.
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00976586
First received: September 10, 2009
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

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.


Condition
Incontinentia Pigmenti

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: In Vitro Observation of Chromosome Recombination and Treatment in Vitro

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Mutation analysis result [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Mutation analysis result


Biospecimen Retention:   Samples With DNA

blood for DNA and plasma. Skin for cultured fibroblast


Enrollment: 50
Study Start Date: August 2009
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Patients wiht Incontinentia Pigmenti
Patients wiht Incontinentia Pigmenti

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients with Incontinentia Pigmenti

Criteria

Inclusion Criteria:

  • Patients diagnosed to have Incontinentia Pigmenti

Exclusion Criteria:

  • None
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00976586

Locations
Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
National Taiwan University Hospital
National Science Council, Taiwan
Investigators
Principal Investigator: NiChung Lee, MD National Taiwan University Hospital
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital, Attending
ClinicalTrials.gov Identifier: NCT00976586     History of Changes
Other Study ID Numbers: 200812061R
Study First Received: September 10, 2009
Last Updated: December 3, 2013
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
Incontinentia pigmenti
recombination
IKBKG
IKBKGP

Additional relevant MeSH terms:
Incontinentia Pigmenti
Abnormalities, Multiple
Congenital Abnormalities
Skin Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Pigmentation Disorders
Skin Diseases

ClinicalTrials.gov processed this record on October 19, 2014