Abstract：
Mutilating palmoplantar keratoderma (PPK) is a heterogeneous genetic disease that poses enormous challenges to clinical diagnosis and genetic counselling. Lanosterol synthase (LSS) gene encodes LSS involved in the biosynthesis pathway of cholesterol. Biallelic mutations in LSS were found to be related to diseases such as cataracts, hypotrichosis and palmoplantar keratoderma-congenital alopecia syndrome. The aim of this study was to investigate the contribution of the LSS mutation to mutilating PPK in a Chinese patient. The clinical and molecular characteristics of the patient were evaluated. A 38-year-old male patient with mutilating PPK was recruited in this study. We identified biallelic variants in the LSS gene (c.683C > T, p.Thr228Ile and c.779G > A, p.Arg260His). Immunoblotting revealed that the Arg260His mutant showed a significantly reduced expression level while Thr228Ile showed an expression level similar to that of the wild type. Thin layer chromatography revealed that mutant Thr228Ile retained partial enzymatic activity and mutant Arg260His did not show any catalytic activity. Our findings show the correlation between LSS mutations and mutilating PPK.
摘要：
残破性掌足底角化病（PPK）是一种异质性遗传疾病，对临床诊断和遗传咨询提出了巨大挑战。羊毛甾醇合酶（LSS）基因编码参与胆固醇生物合成途径的LSS。发现LSS的双等位基因突变与白内障等疾病有关，脱发症和掌plant角化症-先天性脱发综合征。这项研究的目的是研究LSS突变对中国患者PPK致残的贡献。评估患者的临床和分子特征。在这项研究中招募了一名38岁的男性患者，该患者患有PPK。我们鉴定了LSS基因中的双等位基因变体(c.683C>T，p.Thr228Ileandc.779G>A,p.Arg260His)。免疫印迹显示,Arg260His突变体显示显著降低的表达水平,而Thr228Ile显示与野生型相似的表达水平。薄层色谱显示，突变体Thr228Ile保留了部分酶活性，突变体Arg260His未显示任何催化活性。我们的发现显示了LSS突变与PPK突变之间的相关性。
