Copy Number Variations Analysis Identifies QPRT as a Candidate Gene Associated With Susceptibility for Solitary Functioning Kidney

被引：1

作者：

Zhou, Xiao Y. ^{[1
]}

Zheng, Hao Y. ^{[1
]}

Han, Li ^{[1
]}

Wang, Yan ^{[1
]}

Zhang, Li ^{[1
]}

Shu, Xiao M. ^{[1
]}

Zhang, Mu L. ^{[1
]}

Liu, Guan N. ^{[2
]}

Ding, Lian S. ^{[3
]}

机构：

[1] Nanjing Med Univ, Affiliated Huaian Peoples Hosp 1, Dept Obstet, Huaian, Peoples R China

[2] Nanjing Tech Univ, Coll Biol & Pharmaceut Engn, Nanjing, Peoples R China

[3] Nanjing Med Univ, Affiliated Huaian Peoples Hosp 1, Dept Neurosurg, Huaian, Peoples R China

来源：

FRONTIERS IN GENETICS | 2021年 / 12卷

基金：

中国国家自然科学基金;

关键词：

solitary kidney; DNA copy number variations; pentosyltransferases; urogenital abnormalities; cell cycle; TARGET GENE; 16P11.2; MICRODELETION; DEFICIENCY; DELETIONS; DOSAGE;

D O I：

10.3389/fgene.2021.575830

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background The lack of understanding of molecular pathologies of the solitary functioning kidney makes improving and strengthening the continuity of care between pediatric and adult nephrological patients difficult. Copy number variations (CNVs) account for a molecular cause of solitary functioning kidney, but characterization of the pathogenic genes remains challenging. Methods In our prospective cohort study, 99 fetuses clinically diagnosed with a solitary functioning kidney were enrolled and evaluated using chromosomal microarray analysis (CMA). The genetic drivers for the pathogenic CNVs were analyzed. We characterized QPRT localization in fetal kidneys using immunohistochemistry and its expression in adult kidneys using quantitative RT-PCR. Further, QPRT was knocked down using siRNA in human embryonic kidney (HEK293T) cells, and the cell cycle and proliferation were tested. Results Besides one Triple X syndrome and one Down syndrome, we identified a total of 45 CNVs out of 34 subjects. Among the 14 pathogenic CNVs, CNV 16p11.2 reached the highest number of records with the phenotype of kidney anomalies in the Decipher database. Among the 26 genes within the 16p11.2 region, as a key enzyme for nicotinamide adenine dinucleotide (NAD+) biosynthesis, QPRT was distinctly localized in renal tubules but was barely observed in renal interstitial and glomeruli in fetal kidneys. The loss of QPRT prevented cells' efficient transition into S phase, affected cell-cycle progression, and abrogated proliferation of human embryonic kidney cells. Conclusion Our data suggest that QPRT is a candidate gene associated with susceptibility for solitary functioning kidney. The CNVs discovered in our study exhibit great potential for future applications in genetic counseling and pregnancy management.

引用

页数：14