title: A glutamate to lysine mutation at the end of 2B rod domain of keratin 2e gene in ichthyosis bullosa of Siemens.
abstract: Ichthyosis bullosa of Siemens is a rare autosomal dominant skin disorder whose clinical findings are quite similar to those of epidermolytic hyperkeratosis. The differences between those two diseases include absence of erythroderma and different distributions in the skin in ichthyosis bullosa of Siemens. Recent studies have confirmed that ichthyosis bullosa of Siemens is caused by the mutation in the keratin 2e (K2e) gene, which is expressed in the upper spinous and granular layers. We have identified a sporadic case of ichthyosis bullosa of Siemens; based on diagnosis by histopathological findings, the K2e gene of the patient was analysed. Direct sequencing of PCR products revealed a single base change in sequences encoding the highly conserved end of the 2B rod domain segment of the K2e gene. This mutation results in substitution of the codon for glutamic acid by a codon for lysine in position 493 in K2e (E493K). Mutations of the K2e gene involving five different residue positions (Q187P, T485P, L490P, E493D, E493K and E494K) are known to cause ichthyosis bullosa of Siemens. Of these sites, E493, which is conserved in type I and type II keratin genes, is the most frequently altered amino acid in the K2e gene. These data together suggest that this codon constitutes a hot spot for mutations in the K2e gene.
authors.affiliation: Department of Dermatology, College of Medicine, Sungkyunkwan University, Samsung Medical Centre, Seoul, Republic of Korea.
authors.forename: J M
authors.initials: JM
authors.lastname: Yang
authors.forename: E S
authors.initials: ES
authors.lastname: Lee
authors.forename: H J
authors.initials: HJ
authors.lastname: Kang
authors.forename: G S
authors.initials: GS
authors.lastname: Choi
authors.forename: K
authors.initials: K
authors.lastname: Yoneda
authors.forename: S Y
authors.initials: SY
authors.lastname: Jung
authors.forename: K B
authors.initials: KB
authors.lastname: Park
authors.forename: P M
authors.initials: PM
authors.lastname: Steinert
authors.forename: E S
authors.initials: ES
authors.lastname: Lee
mesh_terms: D019943:Amino Acid Substitution; D001483:Base Sequence; D002675:Child, Preschool; D003062:Codon / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D004817:Epidermis / Q000378:metabolism; D005091:Exons / Q000235:genetics; D018698:Glutamic Acid / Q000235:genetics*; D006801:Humans; D017488:Hyperkeratosis, Epidermolytic / Q000235:genetics; D007057:Ichthyosis / Q000235:genetics* / Q000473:pathology; D053557:Keratin-2; D007633:Keratins / Q000235:genetics*; D008239:Lysine / Q000235:genetics*; D008297:Male; D008854:Microscopy, Electron; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D003062:Codon; C089241:KRT2 protein, human; D053557:Keratin-2; D018698:Glutamic Acid; D007633:Keratins; D008239:Lysine