Disturbed keratin expression and distinct genotype of ichthyosis hystrix Lambert type.

We have previously reported the second familial ichthyosis hystrix strongly resembling Lambert type in clinical features, now this family has expanded to three generations, including three patients and five unaffected individuals. The purpose of this study was to investigate the molecular basis of this family. Paraffin-embedded skin sections were stained using keratin 1 (K1), K2, K10, K5+14 and loricrin antibodies. Genomic DNA isolated from blood samples was used to carry out a polymerase-chain-reaction. Immunohistochemistry showed that the distributions, but not the densities of K1/K2/K10 were dramatically changed in the patients. Unlike normal expression of K1/K10 from suprabasal layers and K2 from upper spinous layers, K1/K10 was expressed later from upper spinous layers and K2 was expressed earlier from basal layers; and they were densely aggregated around the nucleus rather than the normal regular distribution in the cytoplasm. DNA sequencing did not reveal any pathogenic mutations in candidate genes (KRT1, KRT2, KRT10 and plakoglobin) in keratin gene clusters. Linkage analysis also excluded the possibility of causative mutations in the epidermal differentiation complex on 1q, desmoplakin gene on 6p and desmosomal cadherin gene cluster on 18q regions. Other genes encoding proteins interacting with keratins might be pathogenic in this rare disease and should be studied further.