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Exome sequencing identifies a COL14A1 mutation in a large Chinese pedigree with punctate palmoplantar keratoderma
  1. Bi-Rong Guo1,2,
  2. Xin Zhang1,2,
  3. Gang Chen2,
  4. Jian-Guo Zhang3,4,
  5. Liang-Dan Sun1,2,
  6. Wei-dong Du2,
  7. Qing Zhang3,
  8. Yong Cui1,2,
  9. Jun Zhu1,2,
  10. Xian-Fa Tang1,2,
  11. Ruo Xiao3,
  12. Yuan Liu1,2,
  13. Min Li1,2,
  14. Hua-Yang Tang1,2,
  15. Xu Yang3,
  16. Hui Cheng1,2,
  17. Ming Li5,
  18. Min Gao1,2,
  19. Ping Li1,2,
  20. Jian-Bo Wang1,2,
  21. Feng-Ping Xu3,
  22. Xian-Bo Zuo2,
  23. Xiao-Dong Zheng2,
  24. Xiao-Guang Zhang1,2,
  25. Lin Yang3,
  26. Jian-Jun Liu2,
  27. Jun Wang3,6,
  28. Sen Yang1,2,
  29. Xue-Jun Zhang1,2
  1. 1Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China
  2. 2State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Hefei, Anhui, China
  3. 3Beijing Genomics Institute-Shenzhen, Shenzhen, China
  4. 4T-Life Research Center, Fudan University Shanghai, China
  5. 5Department of Dermatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  6. 6Department of Biology, University of Copenhagen, Copenhagen, Denmark
  1. Correspondence to Professor Jun Wang, wangj{at}; Professor Sen Yang, yangsen{at}


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.

  • Punctate Palmoplantar Keratoderma
  • Exome Sequencing
  • Mutation
  • COL14A1

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