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

2012; BMJ; Volume: 49; Issue: 9 Linguagem: Inglês

10.1136/jmedgenet-2012-100868

1468-6244

Birong Guo, Xin Zhang, Gang Chen, Jianguo Zhang, Liangdan Sun, Wei‐Dong Du, Qing Zhang, Yong Cui, Jun Zhu, Xianfa Tang, Ruo Xiao, Yuan Liu, Min Li, Huayang Tang, Yang Xu, Hui Cheng, Ming Li, Min Gao, Ping Li, Jianbo Wang, Fengping Xu, Xianbo Zuo, Xiaodong Zheng, Xiaoguang Zhang, Lin Yang, Jianjun Liu, Jun Wang, Sen Yang, Xuejun Zhang,

Plant Reproductive Biology

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.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.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.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.