Papillon-lefèvre Syndrome:CTSC New Mutation Site Report And Literature Review

BackgroundPapillon-Lefèvre syndrome,also known as the syndrome of hyperkeratosis palmoplan and periodontosis(OMIM 245000)is a rare autosomal recessive diso-rder.Its clinical features are palmoplantar keratosis and destructive periodontiti-s in early childhood.More than 300 cases have been reported worldwide.The-re is no definitive study on the etiology and pathogenesis of PLS.Genetic factors and immune factors are considered to be the main causes.It is currently believed that the most important cause of PLS should be related to the mutat e-on of cathepsin C(CTSC)gene.The CTSC gene encodes cathepsin C,also known as dipeptidyl peptidase I,which functions to remove the dipeptide from the amino terminus of the protein substrate,which also has endopeptidase activity.The CTSC gene is usually expressed in the epithelial region,such as the palms,soles,knees,and keratinized oral gums.It is also expressed at high levels in various immune cells,including polymorphonuclear leukocytes,macrophages and their precursor cells.The CTSC gene is involved in a variety of immune and inflammatory responses and plays an important role in the activation of serine proteases.Serine proteases play a major role in a variety of inflammatory and immune processes,including phagocytic destruction of bacteria and activation of phagocytic and T lymphocytes.Therefore,a lack of CTSC function will result in a loss of immune response,leading to the possibility of infection.Currently,the CTSC gene has reported 80 mutations in individuals of different races.We performed a CTSC gene test on a patient with a clinical diagnosis of PLS in the First Affiliated Hospital of Zhengzhou University and found a new mutation site.Objective 1.Summary of a case of PLS patients with history,symptoms,signs,examinations and treatment;2.The CTSC gene sequence analysis of the patient and its parents further confirmed that the mutation of the cathepsin C gene is a clinically dominant cause of PLS;3.Review and analyze the mutation sites reported in previous literature.Methods 1.Clinical data A case of clinical diagnosis of dermatology in the First Affiliated Hospital of Zhengzhou University,a 16-year-old Han male PLS patient,keratosis and desquamation of the hands and feet for more than 10 years,loose teeth,red and swollen gums for 1 year.2.Research method 2.1 Collect blood samples from patients and controls:Extract 5 ml of peripheral venous blood from patients,parents,and 50 healthy adults.2.2 Genomic DNA extraction:Genomic DNA was extracted using the Mag-Bind? Blood and Tissue DNA HDQ 96 kit.2.3 Primer design,synthesis and PCR:Primer5 software was used to design primer sequences,primer synthesis and PCR product sequencing were all completed by Shanghai Shenggong Biological Company.2.4 Gene sequencing analysis: PCR-Sanger sequencing was used to analyze the gene sequences by Sequencing Analysis 5.11 software to determine the mutation sites.2.5 The CTSC locus review has been reported at home and abroad: the relevant literatures were searched by Pubmed,China Knowledge Network and Wanfang Medical Network,and the reported gene loci were statistically analyzed.Results 1.Patient clinical data and treatment effectAdolescent male patients,no obvious cause more than 10 years ago,bilateral palmar skin keratosis,desquamation,posterior wave and metacarpophalangeal joints,interphalangeal joints and knee joint extension,rash increased in autumn and winter.One year ago,some of the teeth were loose,no shedding,with redness and bad breath of the gums,no periodontal empyema.The deciduous teeth and permanent teeth of the patient were normal at the time of eruption,and the deciduous teeth fell off at the age of 4.Dermatology: diffuse erythema,keratinization,increased dermatoglyph,bilateral furrows,partial scaly covering;waxy yellow keratotic plaques in the ankle and heel,mixed with multiple craters Pit;pale red,scaly keratotic plaques can be seen on the metacarpophalangeal joints,interphalangeal joints,and knee joints.Stomatology: gingival congestion and swelling,alveolar bone absorption,atrophy,periodontal pocket formation,with bad breath,no periodontal bleeding and overflow,no tooth loss.There were no obvious abnormalities in the laboratory tests.Oral curved tomography: full mouth alveolar bone has different degrees of absorption,46.47 tooth alveolar bone absorbed to the root tip 1/3,41 tips see low density image.Histopathology of the skin lesions of the hand: the epidermis was significantly hyperkeratotic,the granular layer and the acanthosis were thickened,and the mononuclear cells infiltrated around the superficial blood vessels of the dermis.According to the patient's medical history,symptoms and signs,histopathology and genetic testing,the diagnosis: palmoplantar keratosis periodontitis syndrome.Give Avi A capsules,compound glycyrrhizin tablets orally,and topical compound clobetasol propionate cream.After 1 month of treatment,the patient's skin lesions and oral lesions were alleviated.2.Patients and their parents CTSC gene test resultsCTSC gene detection was performed on patients and their parents.Two heterozygous mutations were identified in the CTSC gene sequencing results.The 1035 th base C of exon 7 was replaced by A(c.1035C>A),and the encoded amino acids were Tyrosine was replaced by a stop codon(p.Tyr345Ter),and the mutation was derived from the father;the 1136 th base A of exon 7 was replaced by T(c.1136A>T),and the encoded amino acid was aspartic acid.Replaced with proline(p.Asp379Val),the variation is derived from the mother.These two mutations were not detected in 50 healthy controls.The above mutations altered the amino acid position of the highly conserved region of the CTSC gene;it was predicted to be detrimental by Mutation Taster(value: 1)and Polyphen-2(score: 1.00).It is speculated that the above mutations are likely to affect the normal function of the CTSC protein,and finally lead to disease.3.CTSC gene mutation site reviewThere are 80 PSC-related CTSC mutations,including missense mutations,nonsense mutations,insertions and deletion mutations.Mutations are mainly distributed in exon 6 and exon 7,which is a highly conserved region of the CTSC gene.Mutations will affect CTSC activity,resulting in almost complete loss of CTSC function in patients with PLS.Conclusion 1.A patient with PLS was diagnosed.2.The new mutation sites of two CTSC genes were found to be c.1035C>A,c.1136A>T,and the CTSC gene mutation was increased to 82,which expanded the mutation spectrum of CTSC gene.