Research On Causal Gene In A Family With Disseminated Superficial Actinic Porokeratosis And Phenoptype Analysis In The Chinese Population

Background Porokeratosis is a series of rare and chronic keratinization disorders and is characterized by lesions with atrophic centers and slightly raised hyperkeratotic edges and a typical histological cornoid lamella.Nearly 20 subtypes of PK have been reported in the literature.Disseminated superficial actinic porokeratosis(DSAP)is the most encountered subtype and typically manifests as multiple small,annular plaques with atrophic centers and slightly raised hyperkeratotic edges.The lesions occur mostly on sun-exposed body areas and can be aggravated by ultraviolet exposure,infections and immunosuppression.Although DSAP has been reported more than 50 years,the molecular mechanisms are not fully understood.Mutations in SLC17A9,MVK,MVD,FDPS and PMVK are reported to be involved in DSAP,among which the MVK and MVD genes were two hotspots mutations.Objectives Sanger sequencing was performed in a Chinese DSAP family to to detect the causative genes.In the meantime,we reviewed the articles reported about DSAP in Chinese population,summarizing their clinical manifestations and discussing the incidence of DSAP in Chinese population,which enhanced our understanding of DSAP.Methods We performed Sanger sequencing and mutational analyses on the MVD and MVK genes to identify the pathogenic mutation in a Chinese family with DSAP.We searched literature for DSAP cases reported in Chinese populations using Sinomed and Pub Med,and summarized its clinical features.Results All of the exons and the exon–intron boundary regions of the MVK gene in 4patients(II 4,III 3,III 9 and IV 5)and 3 controls(III 11,III 13,III 15)were firstly sequenced using Sanger sequencing.However,no associated mutations were identified.Then,we sequenced the MVD gene and identified a c.875A>G(p.Asn292Ser)mutation in exon 7 in the 4 patients;no changes were observed in the 3 unaffected individuals.The study was repeated in other family members of the family,and the results indicated that another 3 affected individuals(III 5,III 7,IV 6)and 4 predicted patients(IV 3,IV 8,IV10 and IV 15)carried this mutation.We did not find the mutations in other individuals in the family.We searched 52 associated literatures,including more than100 families and over 100 sporadic DSAP cases.There were 269 males patients and 199 females patients(male: female = 1.35).The earliest age of onset ranged from 0 to 76 years old,of which the earliest age at onset was 0-52 years in the families and 15-76 years in sporadic patients.DSAP lesions presented on the face were reported in 37 studies,accounting for 71% of the total literature.The lesions were aggravated by sun exposure in 18 studies(34.6%)mostly in summer and reduced in winter.Four studies reported that DSAP patients developed to squamous cell carcinoma(SCC).Some showed comorbidity with LP,PM,SLE,vulgaris pemphigus,psoriasis vulgaris(Ps V),sicca syndrome(SS)and lichenoid amyloidosis.Conclusions We confirmed that c.875A>G mutation of MVD gene was a hotspot mutation.DSAP patients exhibited various clinical features,even if they carried the same mutation.Literature review showed that: the age of onset in DSAP family was earlier than that in sporadic patients;the lesion is common in the face in Chinese population which is distinct from studies in Caucasians;UV exposure is the main aggravating factor.