Abstract：
BACKGROUND: Papillon Lefevre syndrome (PLS) is an autosomal recessive disorder that results from a mutated gene that encodes a lysosomal peptidase known as cathepsin C (CTSC). The clinical presentation of PLS involves mainly palmoplantar keratosis and periodontitis with a variable degree of severity.
METHODS: and methods: Our study included ten patients with a broad spectrum of palmoplantar keratosis and periodontitis severity. CTSC variants were detected by Sanger sequencing. CTSC protein secreted in urine was detected by western blotting.
RESULTS: Five patients have missense variants, Four have nonsense variants, and one has splice variants in CTSC. The activation products of cathepsin C protein (Heavy and light chains) were absent in all patients\' urine samples except one with a significantly reduced level compared to the controls. The dimeric form of CTSC protein was found in all the studied cases. The monomeric form was found in five cases. The products of proteolytic activation of CTSC by other cathepsins (L and S) were found in the urine samples of five of the patients. Each patient had a characteristic pattern of accumulated CTSC protein maturation/activation substrates, intermediates, and products. 40% of the patients had the activation products of other lysosomal cathepsins.
CONCLUSIONS: Urinary CTSC in PLS patients could be used as a diagnostic biomarker for the biochemical screening of the disease. Different variants in CTSC result in different profiles of CTSC secreted in the urine of PLS patients. The profiles of secreted CTSC in urine could be correlated to the severity of palmoplantar keratosis.
METHODS: and methods: Our study included ten patients with a broad spectrum of palmoplantar keratosis and periodontitis severity. CTSC variants were detected by Sanger sequencing. CTSC protein secreted in urine was detected by western blotting.
RESULTS: Five patients have missense variants, Four have nonsense variants, and one has splice variants in CTSC. The activation products of cathepsin C protein (Heavy and light chains) were absent in all patients\' urine samples except one with a significantly reduced level compared to the controls. The dimeric form of CTSC protein was found in all the studied cases. The monomeric form was found in five cases. The products of proteolytic activation of CTSC by other cathepsins (L and S) were found in the urine samples of five of the patients. Each patient had a characteristic pattern of accumulated CTSC protein maturation/activation substrates, intermediates, and products. 40% of the patients had the activation products of other lysosomal cathepsins.
CONCLUSIONS: Urinary CTSC in PLS patients could be used as a diagnostic biomarker for the biochemical screening of the disease. Different variants in CTSC result in different profiles of CTSC secreted in the urine of PLS patients. The profiles of secreted CTSC in urine could be correlated to the severity of palmoplantar keratosis.
摘要：
背景：乳头Lefevre综合征（PLS）是一种常染色体隐性遗传疾病，由编码称为组织蛋白酶C（CTSC）的溶酶体肽酶的突变基因引起。PLS的临床表现主要涉及掌plant角化病和牙周炎，严重程度不同。
方法：和方法：我们的研究纳入了10例广泛患有掌fl角化病和牙周炎严重程度的患者。通过Sanger测序检测CTSC变体。通过蛋白质印迹法检测尿液中分泌的CTSC蛋白。
结果：5例患者有错义变异，四个有废话变体，一个在CTSC中具有剪接变体。组织蛋白酶C蛋白的活化产物（重链和轻链）在所有患者的尿样中都不存在，除了一个与对照组相比水平显着降低。在所有研究的病例中都发现了CTSC蛋白的二聚体形式。在五种情况下发现了单体形式。在五名患者的尿液样品中发现了其他组织蛋白酶（L和S）对CTSC的蛋白水解活化产物。每位患者都有CTSC蛋白成熟/活化底物积累的特征性模式，中间体,和产品。40%的患者具有其他溶酶体组织蛋白酶的活化产品。
结论：PLS患者的尿CTSC可作为诊断性生物标志物用于疾病的生化筛查。CTSC中的不同变体导致PLS患者的尿中分泌的CTSC的不同谱。尿液中分泌的CTSC的分布可能与掌plant角化病的严重程度相关。
方法：和方法：我们的研究纳入了10例广泛患有掌fl角化病和牙周炎严重程度的患者。通过Sanger测序检测CTSC变体。通过蛋白质印迹法检测尿液中分泌的CTSC蛋白。
结果：5例患者有错义变异，四个有废话变体，一个在CTSC中具有剪接变体。组织蛋白酶C蛋白的活化产物（重链和轻链）在所有患者的尿样中都不存在，除了一个与对照组相比水平显着降低。在所有研究的病例中都发现了CTSC蛋白的二聚体形式。在五种情况下发现了单体形式。在五名患者的尿液样品中发现了其他组织蛋白酶（L和S）对CTSC的蛋白水解活化产物。每位患者都有CTSC蛋白成熟/活化底物积累的特征性模式，中间体,和产品。40%的患者具有其他溶酶体组织蛋白酶的活化产品。
结论：PLS患者的尿CTSC可作为诊断性生物标志物用于疾病的生化筛查。CTSC中的不同变体导致PLS患者的尿中分泌的CTSC的不同谱。尿液中分泌的CTSC的分布可能与掌plant角化病的严重程度相关。
