Gene Mutation Analysis Of UROD Gene In Two Pedigree With Porphyria Cutanea Tarda

Background Porphyria cutanea tarda (PCT) is an autosomal dominantinheritance disease characterized by increasing photosensitivity andfrangibility of skin,it often involves in the skin expose to sunshine suchas face、neck and the four limbs.The desease gene of PCT is UROD gene, whichis on chromosome1p34.To date, a total of109mutations in the UROD gene havebeen recorded on the Human Gene Mutation Database.all the mutationsdistribute widely in the gene coding region,there is no obvious mutation hotspots.Objective To study UROD gene mutations in two pedigree with porphyriacutanea tarda, investigate the molecular pathogenesis of the two pedigree.Methods Two family with porphyria cutanea tarda were examined.Bloodsamples were taken from the patients and their family members for genomicDNA preparation.We amplified the total ten exons of UROD gene by polymerasechain reaction and got the sequences of all exons by direct sequencing, thencompared them with the standard sequence of UROD gene that is published onthe NCBI website,(NCBI sequence number:000001.10),in order to find mutationof the UROD gene.Results Five sequence variances were found in the two family:2480T＞A（rs2236576）in the upstream of exon1；3238C＞T（rs12749939）betweenexon one and two;4577G＞T（rs11211066）between exon six and seven;4679G＞T（rs6698485）between exon six and seven;5538C＞T（rs6429553）between exon nine and ten;5634T＞C（rs13948）between exon nine and ten;the above six basedo not encode amino acid.5913G＞A on exon ten，GAA�'AAA，the above nucleotidevariances lead to amino acid substitution:from Glu to Lys. All the sevensingle nucleotide polymorphisms (SNP) can be found in either patients ornormal persons in this pedigree, so no pathopoiesia mutation was found inall exons and their flanking sequences of UROD gene.Conclusions Seven sequence mutations of UROD gene were found in the twopedigree with porphyria cutanea tarda，but the mutations of the exons andtheir flanking sequences of UROD gene were not the reason of the family withporphyria cutanea tarda.The real reason should be looked for outside the tenexons of the UROD gene.