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A Novel Nonsense Mutation at E106 of the 2B Rod Domain of Keratin 14 Causes Dominant Epidermolysis Bullosa Simplex
Author(s) -
Gu LiHong,
Ichiki Yoshiro,
Sato Miki,
Kitajima Yasuo
Publication year - 2002
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/j.1346-8138.2002.tb00236.x
Subject(s) - epidermolysis bullosa simplex , nonsense mutation , missense mutation , keratin 5 , epidermolysis bullosa , keratin 14 , mutation , genetics , biology , keratin , stop codon , mutation testing , microbiology and biotechnology , intermediate filament , gene , cytoskeleton , transgene , genetically modified mouse , cell
Epidermolysis bullosa simplex (EBS) is classified into three main types and is caused, in most case s , by missense mutations in the genes encoding keratin (K) 5 and K14. In this study, we clinically, ultrastructurally, immunohistochemically, and molecularly studied a patient with a dominant EBS, Köbner type. Using sequence analysis of genomic DNA, a novel K14 nonsense mutation was identified. A heterozygous mutation G1231T of KRT14 was found to be associated with the disease in the patient. The mutation created a premature stop codon (amino acid codon 411, residue 106 of the 2B helix) in the K14 molecule. This residue lies in a highly conserved region and was recently found to be absolutely required for molecular stability and intermediate filament assembly in K5 and K14. The E411X (E106X) heterozygous ablation, missing the last 16 amino acid residues of the 2B and the entire tail domain of K14, led to disease but did not result in clumping of keratin filaments. It is the first premature stop codon mutation of K14 found in dominant EBS.