A NOVEL MUTATION IN THE L12 DOMAIN OF KERATIN-5 IN THE KOBNER VARIANTOF EPIDERMOLYSIS-BULLOSA SIMPLEX

Citation
P. Galligan et al., A NOVEL MUTATION IN THE L12 DOMAIN OF KERATIN-5 IN THE KOBNER VARIANTOF EPIDERMOLYSIS-BULLOSA SIMPLEX, Journal of investigative dermatology, 111(3), 1998, pp. 524-527
Citations number
25
Categorie Soggetti
Dermatology & Venereal Diseases
ISSN journal
0022202X
Volume
111
Issue
3
Year of publication
1998
Pages
524 - 527
Database
ISI
SICI code
0022-202X(1998)111:3<524:ANMITL>2.0.ZU;2-9
Abstract
We have identified a novel mutation within the linker L12 region of ke ratin 5 (K5) in a family with the Kobner variant of epidermolysis bull osa simplex. The pattern of inheritance of the disorder in this family is consistent with an autosomal dominant mode of transmission. Affect ed individuals develop extensive and generalized blistering at birth o r early infancy but in later years clinical manifestations are largely confined to palmo-plantar surfaces. Direct sequencing of polymerase c hain reaction products revealed a T to C transition within codon 323 o f K5 in affected individuals, resulting in a valine to alanine substit ution of the seventh residue within the L12 linker domain. This mutati on was not observed in unaffected family members or in 100 K5 alleles of unrelated individuals with normal skin. The other critical regions of K5 and K14 were unremarkable in this family except for common polym orphisms that have been previously described. The valine at position 7 of the L12 domain is absolutely conserved in all type II keratins, an d in other intermediate filament subunits as well, which suggests that this residue makes an important contribution to filament integrity. S econdary structure analysis revealed that alanine at this position mar kedly reduces both the hydrophobicity and the beta-sheet nature of the L12 domain. This is the first report of a mutation at this position i n an intermediate filament subunit and reinforces the importance of th is region to filament biology.