Rare Diseases Symptoms Automatic Extraction

The ichq mutant mouse, a model for the human skin disorder harlequin ichthyosis: mapping, keratinocyte culture, and consideration of candidate genes involved in epidermal growth regulation.

[harlequin ichthyosis]

Harlequin ichthyosis (HI) is a rare and usually fatal scaling skin disorder. The HI mutant mouse (ichq/ichq) has many similarities to the human disorder and provides an important model to identify candidate genes. In this study, we report refined mapping of the mouse ichq locus and consideration of the candidate genes: calpain 1 (Capn1), phospholipase C beta 3 (Plcb3), and Rela and Ikka/Chuk that encode components of the nuclear factor-kappa B (NF-kappaB) pathway. Each are strong candidates because of epidermal expression and/or changes in expression in human HI. All candidates are linked to the ichq locus on mouse Chromosome 19, although Ikka is located more distally. Genetic mapping in mouse has narrowed the ichq critical region to 4 cM. Keratinocytes from skin of +/+, +/ichq and ichq/ichq mice were cultured; all genotypes had similar expression of epidermal differentiation markers. RT-PCR amplification and sequence analysis of each candidate gene did not reveal any mutations in the ichq mouse. Mutational screening of CAPN1 cDNA from different human HI cases revealed a R433P change, but analysis of 50 normal samples demonstrated that this was an apparent polymorphism. Sequence of RELA in five unrelated human HI cases was normal. The results provide compelling evidence that none of these genes are the primary defect in the ichq mouse and that CAPN1 and RELA are not mutated in the human disorder.

Diseases presenting "ichthyosis" symptom

  • child syndrome
  • dystrophic epidermolysis bullosa
  • epidermolysis bullosa simplex
  • harlequin ichthyosis
  • hirschsprung disease
  • junctional epidermolysis bullosa
  • kallmann syndrome
  • lamellar ichthyosis

This symptom has already been validated