title: Ichthyosis bullosa of Siemens--a disease involving keratin 2e.
abstract: Ichthyosis bullosa of Siemens (IBS) is a congenital bullous ichthyosis without erythroderma. In contrast to bullous congenital ichthyosiform erythroderma (BCIE), there is a relatively mild involvement of the skin and epidermolytic hyperkeratosis (EHK) is restricted to the upper suprabasal layers of the epidermis. Tonofilament aggregation was observed by EM in suprabasal cells from affected patients in the two families under study, indicative of a keratin abnormality. Keratin 2e is a differentiation specific type II keratin expressed suprabasally in the epidermis. Part of the K2e gene was amplified by polymerase chain reaction using genomic DNA from affected and unaffected individuals from two IBS families. Direct sequencing of polymerase chain reaction products revealed a point mutation in the highly conserved helix termination motif, producing the protein sequence change LLEGEE-LLEGKE. This mutation was found in all affected members of a five-generation kindred and also in a sporadic case in a second unrelated family. No mutation was seen in unaffected individuals. The mutation destroys a MnlI restriction site, which allowed exclusion of the mutation from a population of 50 unaffected unrelated individuals by restriction fragment analysis of K2e PCR products. This is the sixth keratin gene found to be involved in an inherited epidermal disorder.
authors.affiliation: Department of Anatomy & Physiology, University of Dundee, U.K.
authors.forename: W H
authors.initials: WH
authors.lastname: McLean
authors.forename: S M
authors.initials: SM
authors.lastname: Morley
authors.forename: E B
authors.initials: EB
authors.lastname: Lane
authors.forename: R A
authors.initials: RA
authors.lastname: Eady
authors.forename: W A
authors.initials: WA
authors.lastname: Griffiths
authors.forename: D G
authors.initials: DG
authors.lastname: Paige
authors.forename: J I
authors.initials: JI
authors.lastname: Harper
authors.forename: C
authors.initials: C
authors.lastname: Higgins
authors.forename: I M
authors.initials: IM
authors.lastname: Leigh
mesh_terms: D001483:Base Sequence; D002648:Child; D003937:Diagnosis, Differential; D005260:Female; D006579:Heterozygote; D006801:Humans; D017488:Hyperkeratosis, Epidermolytic / Q000473:pathology; D007057:Ichthyosis / Q000235:genetics* / Q000473:pathology*; D007382:Intermediate Filaments / Q000648:ultrastructure; D053557:Keratin-2; D007633:Keratins / Q000235:genetics*; D008854:Microscopy, Electron; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: C089241:KRT2 protein, human; D053557:Keratin-2; D015335:Molecular Probes; D007633:Keratins