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GENATLAS PHENOTYPE
last update : 15-12-2010
Symbol IP2
Location Xq28
HGNC id 6105
Name incontinentia pigmenti 2
Other name(s) Bloch-Sulzberger syndrome
Corresponding gene IKBKG
Other symbol(s) IP
Main clinical features
  • familial, male-lethal type, X-linked dominant, rare neuro-cutaneous disorder involving skin, teeth, eyes and central nervous system
  • characterized in females by prominent skin signs occuring in four stages : perinatal inflammatory vesicles, verrucous patches of hyperpigmentation and dermal scarring associated with alopecia, invertis/keratitis, hypodontia, the CNS manifestations include seizures, spastic paralysis, microcephaly and mental retardation, eye abnormalities lead to blindness due to retinal detachment
  • most IP females exhibit severely skewed X-inactivation resulting from loss of cells expressing the mutated X-chromosome around birth
    • Genetic determination sex linked
    Function/system disorder dermatology
    eye
    neurology
    Type disease
    Gene product
    Name . NF-kappa B essential modulator
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    unknown   abnormal protein/loss of function amorphic mutations
    deletion     causing inhibition of NEMO-mediated NFKB activation in epidermal keratinocytes and triggering the development of the skin lesions
    Remark(s) . E57K mutation of IKBKG found in a mild form of the genetic disease incontinentia pigmenti, resulted in impaired TRAF6 binding and IL1B signaling (PMID: 20529958))
    Genotype/Phenotype correlations . the variability in IP phenotypes result from a combination of the type of mutation, the functional domain affected and X-inactivation
  • mostly mutations cause frameshift and premature protein truncation leading to loss of function
  • missense mutation of NEMO (A323P) causes a severe form of incontinentia pigmenti
  • duplication (1049dupA) leading to inactive truncated protein with a partial coiled- coil domain, lacking both leucine zipper and zinc finger domains , associated to late inactivation and to immunodeficiency