TY - JOUR 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 SP - 563 LP - 568 DO - 10.1136/jmedgenet-2012-100868 VL - 49 IS - 9 AU - Bi-Rong Guo AU - Xin Zhang AU - Gang Chen AU - Jian-Guo Zhang AU - Liang-Dan Sun AU - Wei-dong Du AU - Qing Zhang AU - Yong Cui AU - Jun Zhu AU - Xian-Fa Tang AU - Ruo Xiao AU - Yuan Liu AU - Min Li AU - Hua-Yang Tang AU - Xu Yang AU - Hui Cheng AU - Ming Li AU - Min Gao AU - Ping Li AU - Jian-Bo Wang AU - Feng-Ping Xu AU - Xian-Bo Zuo AU - Xiao-Dong Zheng AU - Xiao-Guang Zhang AU - Lin Yang AU - Jian-Jun Liu AU - Jun Wang AU - Sen Yang AU - Xue-Jun Zhang Y1 - 2012/09/01 UR - http://jmg.bmj.com/content/49/9/563.abstract N2 - 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. ER -