2. Academic Validation
  3. Exome sequencing identifies a COL14A1 mutation in a large Chinese pedigree with punctate palmoplantar keratoderma

Exome sequencing identifies a COL14A1 mutation in a large Chinese pedigree with punctate palmoplantar keratoderma

  • J Med Genet. 2012 Sep;49(9):563-8. doi: 10.1136/jmedgenet-2012-100868.
Bi-Rong Guo 1,  Xin Zhang,  Gang Chen,  Jian-Guo Zhang,  Liang-Dan Sun,  Wei-Dong Du,  Qing Zhang,  Yong Cui,  Jun Zhu,  Xian-Fa Tang,  Ruo Xiao,  Yuan Liu,  Min Li,  Hua-Yang Tang,  Xu Yang,  Hui Cheng,  Ming Li,  Min Gao,  Ping Li,  Jian-Bo Wang,  Feng-Ping Xu,  Xian-Bo Zuo,  Xiao-Dong Zheng,  Xiao-Guang Zhang,  Lin Yang,  Jian-Jun Liu,  Jun Wang,  Sen Yang,  Xue-Jun Zhang
Affiliations

Affiliation

  • 1 Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China.
PMID: 22972947 DOI: 10.1136/jmedgenet-2012-100868
Abstract

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.

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