Role of Pseudogene in Incontinentia Pigmenti, and Its Potential Treatment

In Vitro Observation of Chromosome Recombination and Treatment in Vitro

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.

Study Overview

• Status: Completed
• Conditions: Incontinentia Pigmenti

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with Incontinentia Pigmenti

Description

Inclusion Criteria:

• Patients diagnosed to have Incontinentia Pigmenti

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients wiht Incontinentia Pigmenti

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: National Science Council, Taiwan
• Investigators: Principal Investigator: NiChung Lee, MD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: September 10, 2009
• First Submitted That Met QC Criteria: September 11, 2009
• First Posted (Estimate): September 14, 2009

Study Record Updates

• Last Update Posted (Estimate): December 4, 2013
• Last Update Submitted That Met QC Criteria: December 3, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Incontinentia pigmenti; recombination; IKBKG; IKBKGP
• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Abnormalities; Abnormalities, Multiple; Pigmentation Disorders; Incontinentia Pigmenti
• Other Study ID Numbers: 200812061R