title: Exome sequencing identifies a COL14A1 mutation in a large Chinese pedigree with punctate palmoplantar keratoderma.
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.
authors.affiliation: Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Bi-Rong
authors.initials: BR
authors.lastname: Guo
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Zhang
authors.forename: Liang-Dan
authors.initials: LD
authors.lastname: Sun
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Du
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Xian-Fa
authors.initials: XF
authors.lastname: Tang
authors.forename: Ruo
authors.initials: R
authors.lastname: Xiao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Hua-Yang
authors.initials: HY
authors.lastname: Tang
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Cheng
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wang
authors.forename: Feng-Ping
authors.initials: FP
authors.lastname: Xu
authors.forename: Xian-Bo
authors.initials: XB
authors.lastname: Zuo
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zheng
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002681:China; D003094:Collagen / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D059472:Exome / Q000235:genetics*; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: C054447:COL14A1 protein, human; D006023:Glycoproteins; D003094:Collagen