PTCH1Gene Mutation In The Sporadic And Familial Basal Cell Nevus Syndrome

BackgroundBasal cell nevus syndrome（BCNS），also referred to as the nevoidbasal cell carcinoma syndrome (NBCCS) or Gorlin-Goltz syndrome(GGS), is an infrequent inherited disease with a broad range of clinicalsymptoms. The assumed prevalence of the disease is1:60,000and thesyndrome is found to occur with an equal frequency in men and women inalmost all ethnic groups except for the Caucasian race, which is most oftenaffected by it. The pathogenesis of BCNS is not completely clear and mostmodern scholars believe that the mutation of PTCH1gene (9q22.3) isresponsible for it while other reports (believed) believe that BCNS,especially accompanied by medulloblastoma and meningioma, might becaused by the mutations of PTCH2and SUFU gene.The clinical manifestations of BCNS are multiple organ dysfunctionand approximately60%of patients reported with multiple mandibularkeratocystic tumor as the first symptoms. The incidence of earlysymptoms of occult, visit lesions often have caused great damage to thejaw area, patients with maxillofacial appearance and masticatory function, influence. Incidence rate of BCNS in patients with medulloblastoma canbe as high as10%. the cause of death is the most important,medulloblastoma is a primary malignant brain tumor, The treatment forBCNS is chemotherapy and postoperative radiotherapy, and becauseBCNS patients is extremely sensitive to radiation therapy, postoperativeradiotherapy will undoubtedly lead to the incidence of cancer increasedbasal cell local. BCNS can be expressed as sporadic and familialaggregation of class two, imaging examination is the family of BCNSpatients and the next generation of screening and early diagnosis of themost important way of checking, has certain limitation, but also increasesthe risk of basal cell carcinoma and other cancers.Therefore, to explore the genetic basis of BCNS, analysis of sporadicand familial aggregation of BCNS phenotype and genetic differences, is ofgreat significance to the family of BCNS patients and the next generationfor early diagnosis, and treatment.ObjectiveTo study the gene mutation analysis of PTCH1in sporadic andfamilial basal cell nevus syndrome.Methods1collection of sporadic basal cell nevus syndrome (2families) andfamilial basal cell nevus syndrome (1families);2Peripheral blood of the three families (experimental group) was collected and genomic DNA was isolated from blood samples. Directsequencing was performed to detect the mutations of PTCH1gene.3Peripheral blood of30healthy people(control group) who were thesame race and region with the experimental group was collected andgenomic DNA was isolated from blood samples. Direct sequencing wasperformed to detect the mutations of PTCH1gene.Results1According to the diagnosis standard amended by Kimonis VEin1997, there were5surviving patients in the familial BCNS(P) and2patients with sporadic BCNS (A. B).The main clinical manifestations weremaxillofacial multiple odontogenic keratocysts, multiple palm pitting,multiple basal cell nevus, cerebral falx, tentorial ectopic calcification,macrocephaly, orbital distance;2One missense mutation (C>T) in exon23（c64244C>T） wasdetected in two sporadic basal cell nevus syndrome and the proband and hischildren of the familial basal cell nevus syndrome, which caused a aminoacid change(p.Leu175Pro).3Another new missense mutation (A>T) in exon22（c62264A>T）was detected in one of the sporadic basal cell nevus syndrome and theproband and his children of the familial basal cell nevus syndrome, whichcaused leucine changed to histidine;4No mutation of PTCH1gene was detected in24healthy people of the three families and the30healthy person of the control group.Conclusions1The pathogenesis of the familial BCNS(P) might be polygenehereditary disease;2The missense mutation (c64244C>T) in the familial BCNS(P)leads to increased susceptibility to the onset of BCNS, but also do noteliminate the root cause of the pedigrees;3The missense mutation (c62264A>T) in sporadic basal cell nevussyndrome (B) patients might be the root cause of the pedigrees;4The clinical manifestations and the incidence of their familieswould be affected by the number of gene mutations in PTCH1withsporadic basal cell nevus syndrome.