Incontinentia Pigmenti Clinical Trial
Official title:
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.
n/a
Observational Model: Cohort, Time Perspective: Prospective
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05954416 -
FARD (RaDiCo Cohort) (RaDiCo-FARD)
|