RT Journal Article
SR Electronic
T1 Exome sequencing identifies a <em>COL14A1</em> mutation in a large Chinese pedigree with punctate palmoplantar keratoderma
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 563
OP 568
DO 10.1136/jmedgenet-2012-100868
VO 49
IS 9
A1 Bi-Rong Guo
A1 Xin Zhang
A1 Gang Chen
A1 Jian-Guo Zhang
A1 Liang-Dan Sun
A1 Wei-dong Du
A1 Qing Zhang
A1 Yong Cui
A1 Jun Zhu
A1 Xian-Fa Tang
A1 Ruo Xiao
A1 Yuan Liu
A1 Min Li
A1 Hua-Yang Tang
A1 Xu Yang
A1 Hui Cheng
A1 Ming Li
A1 Min Gao
A1 Ping Li
A1 Jian-Bo Wang
A1 Feng-Ping Xu
A1 Xian-Bo Zuo
A1 Xiao-Dong Zheng
A1 Xiao-Guang Zhang
A1 Lin Yang
A1 Jian-Jun Liu
A1 Jun Wang
A1 Sen Yang
A1 Xue-Jun Zhang
YR 2012
UL http://jmg.bmj.com/content/49/9/563.abstract
AB Background Punctate palmoplantar keratoderma (PPPK) is a rare autosomal dominant skin disorder characterised by numerous hyperkeratotic papules irregularly distributed on the palms and soles. To date, no causal gene for this disease has been identified. Methods We performed exome sequencing analysis of four affected individuals and two unaffected controls from one Chinese PPPK family where disease locus was mapped at 8q24.13-8q24.21 by our previous linkage analysis. Results We identified a novel heterozygous mutation in COL14A1 gene (c.4505C→T (p.Pro1502Leu)), which located within the linkage region that we previously identified for PPPK. The mutation was shared by the four affected individuals, but not for the two controls of the family. Sanger sequencing confirmed this mutation in another four cases from this family. This mutation was invisible in the normal controls of this family as well as the additional 676 unrelated normal controls and 781 patients with other disease. The shared COL14A1 mutation, p.Pro1502Leu, is a missense substitution at a highly conserved amino acid residue across multiple species. Conclusions The power of combining exome sequencing and linkage information in the study of genetics of autosomal dominant disorders, even in simplex cases, has been demonstrated. Our results suggested that COL14A1 would be a casual gene for PPPK, which was helpful for advancing us on understanding of the pathogenesis of PPPK.