Novel mutations of CTSC Gene in a Chinese PLS patient

Objectives: Papillon-Lefèvre syndrome (PLS, MIM no.245000) is an inherited human disease characterized by early onset periodontitis and abnormal hyperkeratosis of the palms and soles. The incidence of the disease is estimated at 1-4 per million. Mutations in cathepsin C (CTSC) gene have been associated with PLS. To date, more than 40 mutations in the CTSC gene have been identified worldwide, but there is no genetic study of PLS in China. In the present study we investigated the CTSC gene mutations in a Chinese patient affected by PLS.Methods: Patient with PLS from a non-consanguineous family was studied. Peripheral blood samples were collected after informed consent was obtained. Genomic DNA was extracted and seven exons of CTSC gene were amplified by polymerase chain reaction (PCR) using specific primers. Restriction enzymatic digestion was performed when the mutation changed a restriction enzyme site. Results: Sequence analysis of CTSC gene of the PLS patient identified a compound heterozygous mutation: 748 C>T (R250X) and 774 C>G (C258W) which were not detected in normal controls. As heterozygous carrier , the parent were clinically unaffected ,which conformed the recessive nature of PLS. The 748 C>T nonsense mutation produced a premature stop codon at the amino acid position 250 which result in a truncated enzyme of 250 amino acid length in contrast to a normal enzyme of 463 amino acids. The 774 C>G transversion was a novel mutation in CTSC gene affected a highly evolutionarily conserved cysteine residue, and the nucleotide change created a new restriction enzyme site for RsaI.Conclusions: We first report a compound heterozygous patient with PLS in China. The phenotype is the result of CTSC gene mutations in 748 C>T and 774 C>G , and we also identify a novel mutation of CTSC gene 774 C>G (C258W).