Palmoplantar keratoderma, oral involvement, and homozygous <i>CTSC</i> mutation in two brothers from Cambodia

Wei, Heming; Wee, Lynette Wei Yi; Born, Bori; Seang, Sokheng; Koh, Mark Jean‐Aan; Yee, Ruixiang; Lin, Grace; Rafi'ee, Khadijah; Mey, Sithach; Tan, Ene‐Choo

doi:10.1002/ajmg.a.61447

Cited by 4 publications

(2 citation statements)

References 16 publications

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“…Six common candidate genes were observed including CTSC, STAB1, and NCF2. Interestingly, several identified CTSC mutations were previously found to be associated with severe dental caries and periodontitis (Wei et al, 2020); this might explain the correlation between dental caries and periodontal diseases (Mattila et al, 2010;Durand et al, 2019). Also, STAB1 and NCF2 were found to be involved in the activation of macrophages and neutrophils, respectively.…”

Section: Host Genomics and Transcriptomicsmentioning

confidence: 97%

Current State and Challenges of the Global Outcomes of Dental Caries Research in the Meta-Omics Era

Moussa

Ahmad

Mansour

et al. 2022

Front. Cell. Infect. Microbiol.

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Despite significant healthcare advances in the 21st century, the exact etiology of dental caries remains unsolved. The past two decades have witnessed a tremendous growth in our understanding of dental caries amid the advent of revolutionary omics technologies. Accordingly, a consensus has been reached that dental caries is a community-scale metabolic disorder, and its etiology is beyond a single causative organism. This conclusion was based on a variety of microbiome studies following the flow of information along the central dogma of biology from genomic data to the end products of metabolism. These studies were facilitated by the unprecedented growth of the next- generation sequencing tools and omics techniques, such as metagenomics and metatranscriptomics, to estimate the community composition of oral microbiome and its functional potential. Furthermore, the rapidly evolving proteomics and metabolomics platforms, including nuclear magnetic resonance spectroscopy and/or mass spectrometry coupled with chromatography, have enabled precise quantification of the translational outcomes. Although the majority supports ‘conserved functional changes’ as indicators of dysbiosis, it remains unclear how caries dynamics impact the microbiota functions and vice versa, over the course of disease onset and progression. What compounds the situation is the host-microbiota crosstalk. Genome-wide association studies have been undertaken to elucidate the interaction of host genetic variation with the microbiome. However, these studies are challenged by the complex interaction of host genetics and environmental factors. All these complementary approaches need to be orchestrated to capture the key players in this multifactorial disease. Herein, we critically review the milestones in caries research focusing on the state-of-art singular and integrative omics studies, supplemented with a bibliographic network analysis to address the oral microbiome, the host factors, and their interactions. Additionally, we highlight gaps in the dental literature and shed light on critical future research questions and study designs that could unravel the complexities of dental caries, the most globally widespread disease.

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Section: Host Genomics and Transcriptomicsmentioning

confidence: 97%

Current State and Challenges of the Global Outcomes of Dental Caries Research in the Meta-Omics Era

Moussa

Ahmad

Mansour

et al. 2022

Front. Cell. Infect. Microbiol.

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“…What's more, hyperkeratosis can gradually progress other parts of the body, such as the elbows, knees, ankles, and knuckles (Romero‐Quintana et al, 2013 ). Besides, PLS patients often have rapid and severe early‐onset periodontitis and gingivitis, which lead to premature loss of primary and permanent teeth and seriously influence chew function and facial contour (Wei et al, 2020 ). In addition to these basic features, patients with PLS also can present with mild mental retardation, intracranial calcifications, nail dystrophy, etc.…”

Section: Introductionmentioning

confidence: 99%

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

Liu

et al. 2021

Molec Gen & Gen Med

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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.

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The integration of transcriptome-wide association study and mRNA expression profiling data to identify candidate genes and gene sets associated with dental caries

Tong

Hou

et al. 2020

Archives of Oral Biology

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Palmoplantar keratoderma, oral involvement, and homozygous CTSC mutation in two brothers from Cambodia

Cited by 4 publications

References 16 publications

Current State and Challenges of the Global Outcomes of Dental Caries Research in the Meta-Omics Era

Current State and Challenges of the Global Outcomes of Dental Caries Research in the Meta-Omics Era

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

The integration of transcriptome-wide association study and mRNA expression profiling data to identify candidate genes and gene sets associated with dental caries

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