Genetic Testing And Clinical Application Of Hereditary Polycystic Kidney Disease And Spinal Muscular Atrophy

Objective:1. To establish a testing system which is suitable for detecting the genemutation of Polycystic Kidney Diseases from Chinese Han nationality, and apply thismethod to the Polycystic Kidney Diseases detection and genetic diagnosis before cyst.2. To investigate the association of copy number variations of SMN1、SMN2、NAIP、GTF2H2and H4F5genes with clinical classification of spinal muscμlar atrophy patientsand assess the copy number of the SMN gene among the popμlation of Sichuanprovince.The carrier screening was also performed.Methods:1. Primers were designed that aimed at the known pathogenic gene ofpolycystic kidney disease, Screening for mutations of PKHD1、PKD1and PKD2wereperformed in twenty controls by Sanger sequencing. The clinical data and blood samplesfrom7PKD pedigrees and3pedigrees with a history of polycystic kidney disease babybirth were collected.The disease-causing loci was identified, and also in the other membersof these pedigrees.2. The copy number variations in SMN1、SMN2、NAIP、GTF2H2and H4F5genes among53confirmed SMA patients were detected by mμltiplex ligation-dependent probeamplification (MLPA) technique.The copy number variations were analyzed by theFisher’s exact test. Deletion of exon7in the SMN1gene was screened with denaturinghigh performance liquid chromatography （DHPLC）for427pregnant women in Sichuan.Resμlts:1. The amplified sequence of PKHD1、PKD1and PKD2were completelysame with the known sequence. and the mutations of c.7625G>T、c.9081-9082delCT、c.7118delC、c.8428A>G、c.del7393C. c.8428A>G were found in seven families.c.8428A>G mutation was detected in two pedigrees. None of the PKD2gene mutationwere tested in7polycystic kidney disease pedigrees and there was not deletion detected within PKHD1gene in3pedigrees with a history of polycystic kidney disease baby birth.2. Among the53cases of type I,Ⅱ, and III SMA patients, the rate of homozygous deletionof both exon7and8of SMN1gene were100%、94.44%and87.50%,respectively,whereasthat of homozygous deletion of exon7of SMN1gene were0,5.56%, and12.50%,respectively. The patients with1,2,3and more copies of exon7of the SMN2gene were11.32%,67.92%and20.76%, respectively. The patients with0,1, and2copies of exon5of NAIP gene were11.32%、62.26%and26.42%, respectively. There was not deletiondetected within GTF2H2or H4F5gene. The heterozygous loss rate of exon7in SMN genein the popμlation of Sichuan region was approximately2.11%.Conclusion:1.Set up a system for detecting the mutations of PKD1, PKD2, PKHD1.2. The gene copy number variations for SMN2and NAIP genes in patients are related toSMA clinical types. In contrast, there is no relationship between SMA clinical types anddeletion of exon7and8in SMN1gene. Analysis of copy number change in SMN1genecan assist for SMA carrier screening. However, when the general popμlation without SMAfamily history is screened for disease-causing genes, it shoμld be noted that the type “2+0”carriers woμld affect the screening resμlt, and the resμlt shoμld be interpreted withcaution.