Research On Genomic Copy Number Variations Of Congenital Renal Malformations

Congenital Renal Malformations(CRMs)are a part of Congenital Anomalies of the Kidney and Urinary Tract(CAKUT)and are a variety of structural abnormalities characterized by defects in embryonic kidney development.Caused by genetic,epigenetic and environmental factors alone or in interaction,CAKUT is the leading cause of end-stage renal disease in children.Numerous studies have shown that copy number variations(CNVs)in the human genome are associated with birth defects and other diseases.At present,only a small number of potentially pathogenic CNVs and genes associated with CAKUT have been reported in domestic and foreign studies,most of which have not been identified.In addition,researches conducted on solitary CRMs are also relatively few.Based on this point and in order to identify more new potentially pathogenic CNVs and genes associated with solitary CRMs,we collected the blood or tissue samples from 22 cases of fetuses with CRMs and 22 healthy controls in Chinese Han population.Firstly,we used Array-based comparative genomic hybridization(a CGH)to scan and analyze the whole genome of the samples and selected some candidate CNV regions.Then we verified the results of a CGH by CNVplex Genotyping.Finally,we compared the results with databases and identified 17 potentially pathogenic CNV regions and five genes associated with CRMs in 15 cases,from which 10 cases were detected with CNVs in15q11.2,accounting for 47% of all cases.17 potentially pathogenic CNV regions include four known pathogenic CNV regions and 13 novel ones,a total of 25 CNVs and 149 genes,including 12 deletions and 7 duplications.Meanwhile,five potentially pathogenic genes include OR4N4,OR4N3 P,ZDHHC11,LCE3 C and CLDN4 and exit in 15q11.2,1q21.3,5p15.33 and 7q11.23 respectively.In summary,our research and findings can make a preliminary explanation for the causes of solitary CRMs in a genetic point of view and are of great significance in the study of the pathogenesis,prenatal diagnosis and genetic counseling of congenital renal malformations.