A novel missense variant in cathepsin C gene leads to PLS in a Chinese patient: A case report and literature review

Abstract

Background Papilon‐Lefevre syndrome (PLS; OMIM 245000) is a rare autosomal recessive disease characterized by aggressive periodontitis and palmoplantar keratoderma. The prevalence of PLS in the general population is one to four cases per million. Although the etiology and pathogenic mechanisms underlying PLS remain largely unclear, existing evidence shows loss‐of‐function mutations of the cathepsin C gene (CTSC; OMIM 602365) could cause PLS. Here we found a novel variant of the CTSC gene in a Chinese PLS family and predicted the effect of the variant on the physic–chemical characters and tertiary structure of the protein. Methods The 1–7 coding exons and exon–intron boundaries of CTSC gene of the proband and her family were amplified and sequenced directly, and Chromas was used to read sequencing files. Furthermore, the PolyPhen‐2, PROVEAN, and Mutation Taster were utilized to predict the pathogenicity of the variant. Besides, the physic–chemical and structural characters of the protein were analyzed by ProtParam, ProtScale, and SWISS‐MODEL. Results Our study identified a novel homozygous variant c.763T>C (p.Cys255Arg) in exon 6 of the CTSC gene, and it was a likely pathogenic variant as predicted by PolyPhen‐2, PROVEAN, and Mutation Taster. Moreover, ProtParam and Protscale revealed the variant increased the isoelectric point and hydrophilicity of the protein, and the SWISS‐MODEL analysis suggested the variant was located in a critical domain for protein activity. Conclusion Our study analyzed a Chinese family with PLS and identified a novel missense variant in the CTSC gene. Besides, this study retrospectively summarized 113 variants of CTSC in the world and highlighted the features of 27 CTSC variants in Chinese PLS patients. In addition, this study paid much particular attention to the relationship between CTSC variants and different phenotypes.

POU3F3‐related disorder: Defining the phenotype and expanding the molecular spectrum

“…Variants were annotated using the NM_ 006236 (GRCh37/hg19) transcript of POU3F3 . Impact of POU3F3 variants was evaluated by SIFT (sorting intolerant from tolerant), 11 PolyPhen‐2 (polymorphism phenotyping‐v2), 12 CADD v1.6 (combined annotation dependent depletion) 13 and their frequency in Genome Aggregation Database (gnomAD) v2.1.1 14 . Potential splicing effects were assessed using SpliceAI, 15 transcript inferred pathogenicity score 16 and human splicing finder 17 .…”

PIGNencephalopathy: Characterizing the epileptology

“…The cDNA and protein position of the variants was standardized using TransVar 29 . The impact of PIGN variants was assessed using SIFT (Sorting Intolerant From Tolerant), 30 PolyPhen‐2 (Polymorphism Phenotyping‐2), 31 and CADD (Combined Annotation Dependent Depletion), 32 and their frequency in gnomAD (Genome Aggregation Database) 33 . Potential splicing effect was assessed using SpliceAI, 34 transcript inferred pathogenicity score (TraP), 35 and Human Splicing Finder 36 .…”

Functional Study on Cytochrome P450 in Response to L(−)-Carvone Stress in Bursaphelenchus xylophilus

“…A transmembrane structural domain analysis of the proteins determined the function and role of the target protein. ProtScale (https://web.expasy.org/protscale/, accessed on 4 March 2021) [53] was used to analyze the protein hydrophobicity. TMHMM (http://www.cbs.dtu.dk/ser vices/TMHMM, accessed on 4 March 2021) [54] was used to predict the transmembrane helical segments (TMHs) of the protein.…”