Gene Mutations Of Phenylketonuria Children In Ningxia

Objective Phenylketonuria (PKU) is a common autosomal recessive inborn error ofamino acid metabolism and mainly results from deficiency of the phenylalanine hydroxylasegene.The biochemical characteristic of this disease is an elevated concentration ofL-phenylalanine and the metabolite of the bypass in blood serum. Children with Classic PKUneed no-(low) phenylalanine diet therapy all of their life.In addition,some of the childrenneed rehabilitation training to get better recovery.All these brought the family and the societyheavy financial and emotional burden.The incidence of PKU as determined by newborn massscreening in Chinese is1/11180, while the incidence of PKU in Ningxia is1/3065.The ratio ismuch higher than that of the national average.PKU diagnosis in Ningxia is still laggingbehind.It remains at the level of neonatal screening and serological diagnosis, and has not beenyet universal PKU preconception genetic counseling and intervention. In this study, wecharacterized the mutation distribution of the6Exons of PAH gene in Ningxia, and identifiedthe hot spots and regions which are benefited for the early diagnosis，gene diagnoses, geneticscounseling and prenatal diagnosis.By analyzing the relationship between PAH mutationgenotype and biochemical phenotype in order to provide important theoretical basis forclinical develop individualized treatment programs.Methods A total of30children were diagnosed as PKU in Ningxia.Meanwhile,30normal children were served as the controls. Blood samples from the PKU children and theirparents and the normal children were collected.The3、5、6、7、11and12exons of the PAHgene were amplified by the Polymerase chain reaction(PCR)and sequenced.In addition, singlestrand conformation polymorphism(SSCP) were performed.And then,the relationship betweengenotype and biochemical phenotype were studied. Results The6exons and their surrounding introns of the phenylalanine hydroxylase(PAH) gene were detected.Among60alleles,51mutant alleles (85%) were found.A total of16different causative mutations were detected, including missense (n=8), splicing (n=3),nonsense(n=3), Synonymous (n=1)and deletion(n=1).The most common mutations wereR243Q (18.3%), and then Y204C（11.7%）、IVS4-1G＞A（10.0%）、R111X（6.7%）�'�IVS7+2T＞A（6.7%).Among them, two mutations (missense mutation R359K in exon11and deletionmutation N183del in exon6) were novel. Meanwhile we also discovered two polymorphisms(V245V and Q232Q).Furthermore,there are significant correlation between genotype andbiochemical phenotype of PKU.Conclusions By detecting the6hot spot areas of PAH gene in Ningxia PKUchildren,we found obvious hot spot including Y204C、IVS4-1G＞A、R111X and IVS7+2T＞A.We riches the spectrum of Ningxia PAH mutations;.We found2novel mutations,whichexpands the spectrum of Chinese PAH mutations;The testing of the PKU family gene arebenefit for the preconception genetic counseling and intervention to reduce the birth PKUchildren,and thereby reducing the financial and emotional burden on families and society.Byanalyzing the relationship between PKU children genotype and biochemical phenotype,we getimportant theoretical basis for the development of individualized treatment programs.