Abstract: Objective To detect the polymorphisms of the KRT6A and KRT16 genes in two Chinese families with pachyonychia congenita type I, one of which had a family history and another was a sporadic case. Methods All exons and their flanking intronic sequences of the two genes were amplified using polymerase chain reaction and then subjected to automatic DNA sequencing. Restriction analysis was applied to confirm the polymorphisms. Results In the pedigree, a nucleotide (G) deletion in intron sequence between exon 2 and exon 3 of KRT16 gene was detected in the patients. This deletion was also found in the unaffected normal individuals of this family. Meanwhile, the patients were also shown to be carriers of one known single nucleotide polymorphism (SNP), 879 C > T (Asp293Asp) in exon 4 of KRT6A gene. In the sporadic case, a novel non-synonymous SNP, 1252 C > T (R418C), was found in KRT16 gene. This patient was heterozygous while her parents were homozygous for 1252 C and 1252 T, respectively. In addition, two known SNPs, 483 T > C (A161A) and 495 A > G (E165E) in exon 1 of KRT6A gene, were found in this patient. Conclusions A novel single nucleotide polymorphism of KRT16 gene which can result in the change of amino acid sequence is firstly reported and some known single nucleotide polymorphisms in KRT16 and KRT6A genes are also found in this study.

Key words: Pachyonychia congenita, Keratin, Polymorphism, single nucleotide, KRT16, KRT6A