Study On The Mutations Of KRT17 Gene In Chinese Patients With Steatocystoma Multiplex

Background Steatocystoma multiplex is a rare benigh shin appendage tumor characterized by multiple hemispheroid,yellow to skin-colored cystic lesions,which are principally on the trunk and proximal parts of the limbs.The papules can increase in number and size throughout adult life.Onset of the disease tends to occur during adolescence or early adult life.It is thought to be inherited in an autosomal dominant fashion,although many sporadic cases have also been reported.It is demonstrated that steatocystoma multiplex is caused by mutation in KRT17 gene,which is also responsible for Pachyonychia congenital-2.KRT17 is expressed in the nail bed,hair. follicle,sebaceous gland and other epidermal appendages.Each keratin polypeptide possesses a 310-amino acid residueα-helical rod domain that consists of four helical segments named 1A,1B,2A and 2B.The sequences at the beginning of the helix 1A and at the end of the helix 2B are highly conserved and are the most critical for the assembly of the 10-nm intermediate filaments in vivo.KRT17 gene which is 5kb long with 8 exons was mapped to chromosome 17q12-q21.Up to date,there have been 3 germline mutations described in the KRT17 gene in cases of SM,no clear correlation between phenotype and genotypes has been established.In the present study,we have ascertained two Chinese kindreds with steatocystoma multiplex and examined KRT17 gene in these families by direct sequencing.Objective To identify pathogenic mutations of the KRT17 gene in two Chinese kindreds with steatocystoma multiplex. Methods We investigated two Chinese families with SM,collected clinical datas and blood samples from them.Genomic DNA was extracted from peripheral blood of members in two families and 100 unrelated normal controls.All the coding exons and their flanking sequences of KRT17 gene were amplified by polymerase chain reaction (PCR).The PCR products were directly sequenced to detect the mutation.Results One novel KRT17 gene mutation(c.275 A＞G) and one mutation(c.281G＞A) previously described were identified in two Chinese kindreds with steatocystoma multiplex.The two mutations were not found in the healthy members of families and in 100 unrelated control individuals.Conclusions These two missense mutations(c.275A＞G and c.281G＞A) may be the pathogenic mutations in these two Chinese families,not common polymorphism.This study should be useful for genetic counseling,prenatal diagnosis and gene therapy for the patients.