Screening of CTSC gene mutations in a Chinese pedigree affected with Papillon-Lefevre syndrome / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the clinical phenotype of a Chinese pedigree affected with Papillon-Lefevre syndrome(PLS) and detect mutation of CTSC gene.</p><p><b>METHODS</b>Clinical phenotypes were noted, and oral examination for the proband was carried out for the clinical diagnosis of PLS. PCR and Sanger sequencing were used to identify potential mutation of the CTSC gene. Functional effect of the mutation was predicted with SIFT and PolyPhen-2. Swiss-Port was used to predict the tertiary structure of wild type and mutant proteins. The mRNA and protein expression were analyzed by real-time PCR and Western blotting.</p><p><b>RESULTS</b>A homozygous mutation c.901G>A (p.G301S) in exon 7 of CTSC gene was identified in the patient. Both parents of the patient had carried a heterozygous c.901G>A mutation. The mutation was located in the conserved region of CTSC enzyme and was predicted to be damaging by changing the structure of the protein, which could affect the activity of Cathepsin C. However, no significant difference was found in the expression of p.G301S variant at the mRNA and protein levels compared with that of the wild type CTSC gene.</p><p><b>CONCLUSION</b>The c.901G>A mutation of the CTSC gene was first reported in China, which has expanded its mutation spectrum.</p>