Abnormal profiles of cathepsin C secreted in urine of Papillon Lefevre syndrome patients.

Sahar Sabry, Maha Rashed Abouzaid, Mostafa Ibrahim Mostafa, Mohamed Sayed Abdel-Hamid, Ahmed Khairy Saad, Hala Nasr Soliman, Nermeen El-Moataz Bellah Ahmed

European journal of medical genetics 2022 Oct

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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. 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. 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. 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. Copyright © 2022 Elsevier Masson SAS. All rights reserved.

Citation

Sahar Sabry, Maha Rashed Abouzaid, Mostafa Ibrahim Mostafa, Mohamed Sayed Abdel-Hamid, Ahmed Khairy Saad, Hala Nasr Soliman, Nermeen El-Moataz Bellah Ahmed. Abnormal profiles of cathepsin C secreted in urine of Papillon Lefevre syndrome patients. European journal of medical genetics. 2022 Oct;65(10):104605