Abstract | BACKGROUND: OBJECTIVES: To investigate the effects of the novel KRT1:p.Asp340Gly and the one other previously reported KRT1:p.Asp340Val mutations on keratinocyte cytoskeleton formation and stress resistance. METHODS: Wild-type and mutant pEGFP-KRT1 fusion constructs were transfected into HaCaT cells and exposed to hypo-osmotic shock. Haplotyping and genealogical studies were performed to investigate the possibility of a common founder for p.Asp340Gly. RESULTS: Cells transfected with either one of the keratin 1 L12 domain mutations showed significantly increased tonofilament aggregation. The haplotype around the KRT1 gene was shared in all affected family members of two families and a common founder was traced. CONCLUSIONS: Our study supports the pathogenicity of the keratin 1 L12 domain mutations in vitro. These mutations are associated with a milder EI phenotype with pronounced palmoplantar keratoderma, and without neonatal erythroderma and scaling. The KRT1:p.Asp340Gly mutation in the Dutch families is likely to have arisen from a common founder.
|
Authors | M C Bolling, R S Bladergroen, M A M van Steensel, M Willemsen, M F Jonkman, M van Geel |
Journal | The British journal of dermatology
(Br J Dermatol)
Vol. 162
Issue 4
Pg. 875-9
(Apr 2010)
ISSN: 1365-2133 [Electronic] England |
PMID | 20500210
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
|
Topics |
- Chromosome Mapping
- DNA Mutational Analysis
- Female
- Humans
- Hyperkeratosis, Epidermolytic
(genetics, pathology)
- Keratin-1
(genetics)
- Male
- Mutation, Missense
(genetics)
- Netherlands
- Pedigree
- Phenotype
|