Wen-Ting Liu and Hai-Ping Ke contributed equally to this work.
The Most Common Mutation of KRT9, c.C487T (p.R163W), in Epidermolytic Palmoplantar Keratoderma in Two Large Chinese Pedigrees
Version of Record online: 20 JAN 2012
Copyright © 2012 Wiley Periodicals, Inc.
The Anatomical Record
Volume 295, Issue 4, pages 604–609, April 2012
How to Cite
Liu, W.-T., Ke, H.-P., Zhao, Y., Chen, X.-L., Lu, J.-J., Du, Z.-F., Yu, D. and Zhang, X.-N. (2012), The Most Common Mutation of KRT9, c.C487T (p.R163W), in Epidermolytic Palmoplantar Keratoderma in Two Large Chinese Pedigrees. Anat Rec, 295: 604–609. doi: 10.1002/ar.22409
- Issue online: 12 MAR 2012
- Version of Record online: 20 JAN 2012
- Manuscript Accepted: 8 DEC 2011
- Manuscript Received: 28 SEP 2011
- National Natural Science Foundation of China. Grant Numbers: 30972644, J0710043
- epidermolytic palmoplantar keratoderma;
- Keratin 9;
- KRT9 gene;
- missense mutation;
Epidermolytic palmoplantar keratoderma (EPPK) is generally associated with dominant-negative mutations of the Keratin 9 gene (KRT9), and rarely with the Keratin 1 gene (KRT1). To date, a myriad of mutations has been reported with a high frequency of codon 163 mutations within the first exon of KRT9 in different populations. Notably, a distinct phenotypic heterogeneity, digital mutilation, was found recently in a 58-year-old female Japanese EPPK patient with p.R163W. Here, we report the most common mutation, c.C487T (p.R163W) of KRT9, in two large EPPK pedigrees from southeast China. The arginine residue in peptide position 163 remains almost constant in at least 47 intermediate filament proteins ranging from snail to human. A substitution in arginine alters both the charge and shape of the 1A rod domain and disrupts the function of the helix initiation motif of keratins, finally compromising the integrity of filaments and weakening their stability in the epidermis of palms and soles. We summarize the clinical symptoms of EPPK in Chinese and show that knuckle pads are associated with KRT9 mutations. We suggest that the frequency of p.R163W in Chinese EPPK patients (31.03%) is consistent with that in the general population (29.33%), and that codon 163 is truly a hotspot mutational site of KRT9. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.