掌跖角化牙周病综合征患者组织蛋白酶C基因的新突变

目的探讨掌跖角化牙周病综合征又称帕-勒综合征(PLS)患者组织蛋白酶 C 基因(CTSC)突变的特点,为该病发生的分子机制研究提供依据。方法对临床诊断为 PLS 的2例患者进行 CTSC 基因突变的分析。分别提取患者及其父母的基因组 DNA,应用聚合酶链反应和 DNA 直接测序进行基因突变的检测,进一步采用限制性内切酶酶切验证突变。结果 2例 PLS 患者均存在 CTSC基因的复合型杂合突变,患者Ⅰ的突变位点为 G139R 和S260P,患者Ⅱ的突变位点为 R250X 和C258W,健康对照组未发现基因突变,其中 S260P 和 C258W 突变是 CTSC 基因的新突变位点。结论CTSC 基因突变是导致2例 PLS 患者临床表型的致病原因,S260P 和 C258W 突变扩大了 CTSC 基因的突变谱,为我国 PLS 疾病的基因诊断提供了依据。

Novel mutations of cathepsin C gene in two Chinese patients with Papillon-Lefèvre syndrome

OBJECTIVE: To investigate the mutational characteristics of cathepsin C (CTSC) gene in two Chinese patients with Papillon-Lefèvre syndrome (PLS), and provide molecular basis for research of the pathogenesis of PLS. METHODS: Peripheral blood samples were obtained from patients and their parents respectively. Genomic DNA were extracted after consents. Polymerase chain reaction, direct DNA sequencing and restriction enzyme reaction were performed to screen mutations of CTSC gene. RESULTS: Compound heterozygous mutations of CTSC gene were identified in the two patients. Patient I carried the G139R and S260P mutations, patient II had the R250X and C258W mutations. The parents were heterozygous carriers without the clinical feature of PLS. None of the mutations were detected in normal controls. Furthermore, the S260P and C258W changes were novel mutations of CTSC gene, which had not been reported previously. CONCLUSIONS: Mutations of CTSC gene are responsible for the phenotype of Papillon-Lefèvre syndrome in two Chinese patients. The results extend the mutation spectrum of CTSC gene and also provide basis for gene diagnosis of PLS in China.