A novel large deletion combined with a nonsense mutation in a <scp>C</scp>hinese child with <scp>P</scp>apillon–<scp>L</scp>efèvre syndrome

Wu, Wei; Chen, Bin J. W.; Chen, Xi; Chen, L.; Yi, Long; Wang, Y.; Yan, Fuhua; Sun, Weibin

doi:10.1111/jre.12317

Cited by 5 publications

(7 citation statements)

References 13 publications

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“…Among the Chinese patients with CTSC gene variants, one patient showed physical retardation (Wu et al, 2019 ). It was worth noting that one patient manifested skin abnormalities at 1 week after she was born, and this finding was earlier than most previous reports (Wu et al, 2016 ). In addition, Wang et al first reported that serum levels of IgE were significantly increased in a PLS patient and the serum IgE subsequently decreased in tune with the recovery of periodontitis (Wang et al, 2015 ; Wen et al, 2012 ).…”

Section: Discussionsupporting

confidence: 46%

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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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Section: Discussionsupporting

confidence: 46%

“…In addition to these basic features, patients with PLS also can present with mild mental retardation, intracranial calcifications, nail dystrophy, etc. About 20%–25% of PLS patients increased susceptibility to microbial infections, such as skin abscess, kidney abscess, or liver abscess (Wu et al, 2016 , 2019 ).…”

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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“…Cathepsin C activity is proposed to play a key role in the epithelial differentiation and desquamation, while the inappropriate genetic alterations may result in nearly complete loss of cathepsin C enzymatic activity in homozygous individuals with the disease, or correspondently reduced activity of the enzyme in the family members who are heterozygous carriers [36,37]. The present research group reported a PLS patient with a 110 kb deletion (Chr11: 88032292:88142997 [NC_000011]) and a nonsense mutation exists (Gln182Ter, CAG > TAG) in the fourth exon of the CTSC gene [38].…”

Section: Etiology and Pathogenesismentioning

confidence: 87%

“…Patients with PLS present first clinical signs in the oral cavity as soon as the deciduous teeth erupt [34,36]. Oral manifestations become apparent by the age of 2 to 3 years with rapid periodontal destruction: plaque accumulation, obvious gingival inflammation and bleeding, periodontal abscess, deep periodontal pocket formation, alveolar bone resorption, loose teeth, halitosis, following by premature exfoliation of all deciduous teeth by the age of 4 to 5 years (Figure 7) [38]. Radiographic investigations show generalized alveolar bone loss and migration of teeth whit no evidence of root resorption (Figure 8).…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Periodontal Disease Associated with Genetic Disorders

Wu¹,

Leung²,

Sun³

2022

Dentistry

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The object of this chapter was to provide an overview including relevant research progress of some genetic disorders with periodontal manifestations. A number of genetic disorders increase patient susceptibility to periodontal disease, with the latter exhibit rather rapid and aggressive presentations. Periodontal disease, perhaps could be the first detectable sign of an undiagnosed genetic disorder. It is therefore important for dental practitioners to be familiar with genetic disorders and their impact on the periodontal tissues. This chapter reviews several genetic disorders that exhibit periodontal manifestations, including hereditary gingival fibromatosis, Papillon-Lefèvre syndrome, cyclic neutropenia, Ehlers-Danlos syndrome and hypophosphatasia.

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“…Other symptoms of PLS are hyperhidrosis, intracranial calcification, arachnodactyly, increased susceptibility to infections, hearing loss, mental retardation, oculocutaneous albinism, bent nail syndrome, corneal cell hyperkeratosis, acanthosis nigricans, thicker cutaneous granular layer, etc (Almuneef, Al Khenaizan, Al Ajaji, & Al-Anazi, 2003;Borroni et al, 1985;Farkas et al, 2013;Haneke, 1979;Khandpur & Reddy, 2001;Oguzkurt, Tanyel, Büyükpamukçu, & Hiçsönmez, 1996;Basapogu Sreeramulu et al, 2015;Tosti, Manuzzi, Bardazzi, & Costa, 1988;Wani, Devkar, Patole, & Shouche, 2006;Wu et al, 2016). Furthermore, this disorder may also be accompanied with other symptoms such as the skin, liver, kidneys and brain abscesses(R J Gorlin et al, 1964;Kanthimathinathan et al, 2013;Mercy, Singh, Ghorpade, Das, & Upadhyay, 2013;Morgan, Hannon, & Lakhoo, 2011).…”

Section: Introductionmentioning

confidence: 99%

A novel mutation in the CTSC gene in Iranian family with Papillon-Lefevre Syndrome

Ghanei¹,

Abbaszadegan²,

Forghanifard³

et al.

Authorea

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Background: PLS is a rare autosomal recessive disorder characterized by the palmar-plantar hyperkeratosis and severe degeneration of the periodontium. The defects in cathepsin C gene, are responsible for PLS. In this study, we analyzed the whole exomes of CTSC gene in a family with history of PLS. Methods: Genomic DNA was extracted from peripheral blood and genotype analysis was performed. The mutated protein sequence was used to find the best possible tertiary structure for homology modeling. The homology modeling of the novel mutation was then performed using the online Swiss-Prot server. The results were also analyzed for to verify its validity. Results: The analysis of CTSC gene elucidated a novel insertion GAC. The novel mutation was proved by analyzing 50 healthy control volunteers. Modeling of the novel found mutation in CTSC gene revealed structural defects that may have caused the functional abnormalities. Discussion: The structural analysis of the mutated protein model identifies changes in the stereo-chemical and the energy level of the mutated protein. Since this protein play a role in the activation of granule serine proteases from cytotoxic T lymphocytes, natural killer cells, mast cells, such structural defects may lead to its malfunction causing dysfunctioning of immune defense mechanisms.

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A novel large deletion combined with a nonsense mutation in a Chinese child with Papillon–Lefèvre syndrome

Abstract: Our study reveals a compound mutation consisting of a large deletion and a nonsense mutation, which provides a new insight in the mutation type of CTSC gene.

Cited by 5 publications

References 13 publications

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

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

Periodontal Disease Associated with Genetic Disorders

A novel mutation in the CTSC gene in Iranian family with Papillon-Lefevre Syndrome

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