Abstract
Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; and vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12 and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1-p16.3 and 22q11.2 were specific for KA; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Data availability
Raw data that support the findings of this study will in part be available from the corresponding authors upon reasonable request and are in part available from dbGaP (https://www.ncbi.nlm.nih.gov/gap; accession pending). Some restrictions may apply according to participants’ consent and privacy protection. All images generated from mouse experiments reported in this study will also be available from the corresponding authors upon reasonable request.
References
Wuhl, E. et al. Timing and outcome of renal replacement therapy in patients with congenital malformations of the kidney and urinary tract. Clin. J. Am. Soc. Nephrol. 8, 67–74 (2013).
Chesnaye, N. C. et al. Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe: an ESPN-ERA/EDTA registry analysis. Lancet 389, 2128–2137 (2017).
Sanna-Cherchi, S. et al. Renal outcome in patients with congenital anomalies of the kidney and urinary tract. Kidney Int. 76, 528–533 (2009).
Goodyer, P. R. Renal dysplasia/hypoplasia. in Pediatric Nephrology 5th edn. (eds. Avner, E. D., Harmon, W. E. & Niaudet, P.) 83–91 (Lippincott Williams & Wilkins, Philadelphia, 2004).
Sanna-Cherchi, S., Westland, R., Ghiggeri, G. M. & Gharavi, A. G. Genetic basis of human congenital anomalies of the kidney and urinary tract. J. Clin. Invest. 128, 4–15 (2018).
Schedl, A. Renal abnormalities and their developmental origin. Nat. Rev. Genet. 8, 791–802 (2007).
Costantini, F. & Kopan, R. Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Dev. Cell. 18, 698–712 (2010).
Short, K. M. & Smyth, I. M. The contribution of branching morphogenesis to kidney development and disease. Nat. Rev. Nephrol. 12, 754–767 (2016).
dos Santos Junior, A. C., de Miranda, D. M. & Simoes e Silva, A. C. Congenital anomalies of the kidney and urinary tract: an embryogenetic review. Birth Defects Res. C. Embryo Today 102, 374–381 (2014).
Chen, F. Genetic and developmental basis for urinary tract obstruction. Pediatr. Nephrol. 24, 1621–1632 (2009).
Vainio, S. & Lin, Y. Coordinating early kidney development: lessons from gene targeting. Nat. Rev. Genet. 3, 533–543 (2002).
Sanna-Cherchi, S. et al. Genetic approaches to human renal agenesis/hypoplasia and dysplasia. Pediatr. Nephrol. 22, 1675–1684 (2007).
Nicolaou, N., Renkema, K. Y., Bongers, E. M., Giles, R. H. & Knoers, N. V. Genetic, environmental, and epigenetic factors involved in CAKUT. Nat. Rev. Nephrol. 11, 720–731 (2015).
Georgas, K. M. et al. An illustrated anatomical ontology of the developing mouse lower urogenital tract. Development 142, 1893–1908 (2015).
Thomas, R. et al. HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort. Pediatr. Nephrol. 26, 897–903 (2011).
Weber, S. et al. Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: results of the ESCAPE study. J. Am. Soc. Nephrol. 17, 2864–2870 (2006).
Nicolaou, N. et al. Prioritization and burden analysis of rare variants in 208 candidate genes suggest they do not play a major role in CAKUT. Kidney Int. 89, 476–486 (2016).
Sanna-Cherchi, S. et al. Mutations in DSTYK and dominant urinary tract malformations. N. Engl. J. Med. 369, 621–629 (2013).
Vivante, A. et al. Mutations in TBX18 cause dominant urinary tract malformations via transcriptional dysregulation of ureter development. Am. J. Hum. Genet. 97, 291–301 (2015).
Schimmenti, L. A. et al. Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations. Am. J. Hum. Genet. 60, 869–878 (1997).
Bekheirnia, M. R. et al. Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene. Genet. Med. 19, 412–420 (2017).
Ichikawa, I., Kuwayama, F., Pope, J. Ct, Stephens, F. D. & Miyazaki, Y. Paradigm shift from classic anatomic theories to contemporary cell biological views of CAKUT. Kidney Int. 61, 889–898 (2002).
Lopez-Rivera, E. et al. Genetic drivers of kidney defects in the DiGeorge syndrome. N. Engl. J. Med. 376, 742–754 (2017).
Hwang, D. Y. et al. Mutations in 12 known dominant disease-causing genes clarify many congenital anomalies of the kidney and urinary tract. Kidney Int. 85, 1429–1433 (2014).
Vivante, A., Kohl, S., Hwang, D. Y., Dworschak, G. C. & Hildebrandt, F. Single-gene causes of congenital anomalies of the kidney and urinary tract (CAKUT) in humans. Pediatr. Nephrol. 29, 695–704 (2014).
Sanna-Cherchi, S. et al. Copy-number disorders are a common cause of congenital kidney malformations. Am. J. Hum. Genet. 91, 987–997 (2012).
Verbitsky, M. et al. Genomic imbalances in pediatric patients with chronic kidney disease. J. Clin. Invest. 125, 2171–2178 (2015).
Westland, R. et al. Copy number variation analysis identifies novel CAKUT candidate genes in children with a solitary functioning kidney. Kidney Int. 88, 1402–1410 (2015).
Ulinski, T. et al. Renal phenotypes related to hepatocyte nuclear factor-1beta (TCF2) mutations in a pediatric cohort. J. Am. Soc. Nephrol. 17, 497–503 (2006).
Madariaga, L. et al. Severe prenatal renal anomalies associated with mutations in HNF1B or PAX2 genes. Clin. J. Am. Soc. Nephrol. 8, 1179–1187 (2013).
Hoskins, B. E. et al. Missense mutations in EYA1 and TCF2 are a rare cause of urinary tract malformations. Nephrol. Dial. Transplant. 23, 777–779 (2008).
Heidet, L. et al. Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases. Clin. J. Am. Soc. Nephrol. 5, 1079–1090 (2010).
Carvalho, C. M. & Lupski, J. R. Mechanisms underlying structural variant formation in genomic disorders. Nat. Rev. Genet. 17, 224–238 (2016).
Lupski, J. R. Genomic disorders: structural features of the genome can lead to DNA rearrangements and human disease traits. Trends Genet. 14, 417–422 (1998).
Miller, D. T. et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am. J. Hum. Genet. 86, 749–764 (2010).
South, S. T. et al. ACMG Standards and Guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013. Genet. Med. 15, 901–909 (2013).
Swaminathan, G. J. et al. DECIPHER: web-based, community resource for clinical interpretation of rare variants in developmental disorders. Hum. Mol. Genet. 21, R37–R44 (2012).
Firth, H. V. et al. DECIPHER: database of chromosomal imbalance and phenotype in humans using Ensembl resources. Am. J. Hum. Genet. 84, 524–533 (2009).
Grisaru, S., Ramage, I. J. & Rosenblum, N. D. Vesicoureteric reflux associated with renal dysplasia in the Wolf-Hirschhorn syndrome. Pediatr. Nephrol. 14, 146–148 (2000).
Mefford, H. C. et al. Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy. Am. J. Hum. Genet. 81, 1057–1069 (2007).
Portnoi, M. F. Microduplication 22q11.2: a new chromosomal syndrome. Eur. J. Med. Genet. 52, 88–93 (2009).
Kobrynski, L. J. & Sullivan, K. E. Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet 370, 1443–1452 (2007).
Weber, S. et al. Mapping candidate regions and genes for congenital anomalies of the kidneys and urinary tract (CAKUT) by array-based comparative genomic hybridization. Nephrol. Dial. Transplant. 26, 136–143 (2011).
Hildebrandt, F. et al. A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1. Nat. Genet. 17, 149–153 (1997).
Willatt, L. et al. 3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome. Am. J. Hum. Genet. 77, 154–160 (2005).
Mattina, T., Perrotta, C. S. & Grossfeld, P. Jacobsen syndrome. Orphanet. J. Rare. Dis. 4, 9 (2009).
Sampson, M. G. et al. Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung disease. Am. J. Med. Genet. A 152A, 2618–2622 (2010).
Fontes, M. I. et al. Genotype-phenotype correlation of 16p13.3 terminal duplication and 22q13.33 deletion: Natural history of a patient and review of the literature. Am. J. Med. Genet. A 170, 766–772 (2016).
Goh, E. S. et al. Definition of a critical genetic interval related to kidney abnormalities in the Potocki-Lupski syndrome. Am. J. Med. Genet. A 158A, 1579–1588 (2012).
Yamamoto, T. et al. A large interstitial deletion of 17p13.1p11.2 involving the Smith-Magenis chromosome region in a girl with multiple congenital anomalies. Am. J. Med. Genet. A 140, 88–91 (2006).
Kim, Y. M. et al. Phelan-McDermid syndrome presenting with developmental delays and facial dysmorphisms. Korean J. Pediatr. 59, S25–S28 (2016).
Ozgun, M. T. et al. Prenatal diagnosis of a fetus with partial trisomy 7p. Fetal. Diagn. Ther. 22, 229–232 (2007).
Trachoo, O., Assanatham, M., Jinawath, N. & Nongnuch, A. Chromosome 20p inverted duplication deletion identified in a Thai female adult with mental retardation, obesity, chronic kidney disease and characteristic facial features. Eur. J. Med. Genet. 56, 319–324 (2013).
Westland, R. et al. Phenotypic expansion of DGKE-associated diseases. J. Am. Soc. Nephrol. 25, 1408–1414 (2014).
Karczewski, K. J. et al. The ExAC browser: displaying reference data information from over 60,000 exomes. Nucleic Acids Res. 45, D840–D845 (2017).
Lek, M. et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536, 285–291 (2016).
Materna-Kiryluk, A. et al. The emerging role of genomics in the diagnosis and workup of congenital urinary tract defects: a novel deletion syndrome on chromosome 3q13.31-22.1. Pediatr. Nephrol. 29, 257–267 (2014).
Lata, S. et al. Whole-exome sequencing in adults with chronic kidney disease: A pilot study. Ann. Intern. Med. 168, 100–109 (2018).
Wu, N. et al. TBX6 null variants and a common hypomorphic allele in congenital scoliosis. N. Engl. J. Med. 372, 341–350 (2015).
Al-Kateb, H. et al. Scoliosis and vertebral anomalies: additional abnormal phenotypes associated with chromosome 16p11.2 rearrangement. Am. J. Med. Genet. A 164A, 1118–1126 (2014).
Dickinson, M. E. et al. High-throughput discovery of novel developmental phenotypes. Nature 537, 508–514 (2016).
Chapman, D. L. & Papaioannou, V. E. Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6. Nature 391, 695–697 (1998).
Chapman, D. L., Agulnik, I., Hancock, S., Silver, L. M. & Papaioannou, V. E. Tbx6, a mouse T-Box gene implicated in paraxial mesoderm formation at gastrulation. Dev. Biol. 180, 534–542 (1996).
Abe, K. et al. Novel ENU-induced mutation in Tbx6 causes dominant spondylocostal dysostosis-like vertebral malformations in the rat. PLoS ONE. 10, e0130231 (2015).
Lefebvre, M. et al. Autosomal recessive variations of TBX6, from congenital scoliosis to spondylocostal dysostosis. Clin. Genet. 91, 908–912 (2017).
Sparrow, D. B. et al. Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6. Hum. Mol. Genet. 22, 1625–1631 (2013).
MacEwen, G. D., Winter, R. B., Hardy, J. H. & Sherk, H. H. Evaluation of kidney anomalies in congenital scoliosis. 1972. Clin. Orthop. Relat. Res. 434, 4–7 (2005).
Cowell, H. R., MacEwen, G. D. & Hubben, C. Incidence of abnormalities of the kidney and ureter in congenital scoliosis. Birth Defects. Orig. Artic. Ser. 10, 142–145 (1974).
MacEwen, G. D., Winter, R. B. & Hardy, J. H. Evaluation of kidney anomalies in congenital scoliosis. J. Bone Joint Surg. Am. 54, 1451–1454 (1972).
Hadjantonakis, A. K., Pisano, E. & Papaioannou, V. E. Tbx6 regulates left/right patterning in mouse embryos through effects on nodal cilia and perinodal signaling. PLoS ONE. 3, e2511 (2008).
Watabe-Rudolph, M., Schlautmann, N., Papaioannou, V. E. & Gossler, A. The mouse rib-vertebrae mutation is a hypomorphic Tbx6 allele. Mech. Dev. 119, 251–256 (2002).
Batourina, E. et al. Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret. Nat. Genet. 32, 109–115 (2002).
Batourina, E. et al. Vitamin A controls epithelial/mesenchymal interactions through Ret expression. Nat. Genet. 27, 74–78 (2001).
Batourina, E. et al. Apoptosis induced by vitamin A signaling is crucial for connecting the ureters to the bladder. Nat. Genet. 37, 1082–1089 (2005).
Harambat, J., van Stralen, K. J., Kim, J. J. & Tizard, E. J. Epidemiology of chronic kidney disease in children. Pediatr. Nephrol. 27, 363–373 (2012).
Westland, R., Kurvers, R. A., van Wijk, J. A. & Schreuder, M. F. Risk factors for renal injury in children with a solitary functioning kidney. Pediatrics 131, e478–e485 (2013).
Westland, R., Schreuder, M. F., Bokenkamp, A., Spreeuwenberg, M. D. & van Wijk, J. A. Renal injury in children with a solitary functioning kidney: the KIMONO study. Nephrol. Dial. Transplant. 26, 1533–1541 (2011).
Westland, R., Schreuder, M. F., van Goudoever, J. B., Sanna-Cherchi, S. & van Wijk, J. A. Clinical implications of the solitary functioning kidney. Clin. J. Am. Soc. Nephrol. 9, 978–986 (2014).
Verbitsky, M. et al. Genomic disorders and neurocognitive impairment in pediatric CKD. J. Am. Soc. Nephrol. 28, 2303–2309 (2017).
Cooper, G. M. et al. A copy number variation morbidity map of developmental delay. Nat. Genet. 43, 838–846 (2011).
Greenway, S. C. et al. De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot. Nat. Genet. 41, 931–935 (2009).
Osoegawa, K. et al. Identification of novel candidate genes associated with cleft lip and palate using array comparative genomic hybridisation. J. Med. Genet. 45, 81–86 (2008).
Serra-Juhe, C. et al. Contribution of rare copy number variants to isolated human malformations. PLoS ONE. 7, e45530 (2012).
Brunetti-Pierri, N. et al. Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities. Nat. Genet. 40, 1466–1471 (2008).
Sanders, S. J. et al. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 70, 863–885 (2011).
Sebat, J. et al. Strong association of de novo copy number mutations with autism. Science 316, 445–449 (2007).
Stefansson, H. et al. Large recurrent microdeletions associated with schizophrenia. Nature 455, 232–236 (2008).
Yu, L. et al. De novo copy number variants are associated with congenital diaphragmatic hernia. J. Med. Genet. 49, 650–659 (2012).
Mannik, K. et al. Copy number variations and cognitive phenotypes in unselected populations. JAMA 313, 2044–2054 (2015).
Golzio, C. & Katsanis, N. Genetic architecture of reciprocal CNVs. Curr. Opin. Genet. Dev. 23, 240–248 (2013).
Golzio, C. et al. KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant. Nature 485, 363–367 (2012).
Gandelman, K. Y., Gibson, L., Meyn, M. S. & Yang-Feng, T. L. Molecular definition of the smallest region of deletion overlap in the Wolf-Hirschhorn syndrome. Am. J. Hum. Genet. 51, 571–578 (1992).
Driscoll, D. A., Budarf, M. L. & Emanuel, B. S. A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11. Am. J. Hum. Genet. 50, 924–933 (1992).
Concepcion, D. et al. Cell lineage of timed cohorts of Tbx6-expressing cells in wild-type and Tbx6 mutant embryos. Biol. Open 6, 1065–1073 (2017).
Wang, K. et al. PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. Genome Res. 17, 1665–1674 (2007).
Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).
Price, A. L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).
Fasel, D., Verbitsky, M. & Sanna-Cherchi, S. CNVkit: software tools for analyzing genomic structural variants. J. Am. Soc. Nephrol. 26 (Abstract edition), 443A (2015).
Wickham, H. ggplot2: Elegant Graphics for Data Analysis (Springer, New York, 2009).
McKinney, W. Data Structures for Statistical Computing in Python. in Proc. 9th Python in Sci. Conference (eds. van der Walt, S. & Millman, J.) 51–56 (Austin, Texas, USA, 2010).
Acknowledgements
We thank all patients and family members for participating in this study. We thank J. R. Lupski for critical review of this manuscript. This work was supported by grants (1R01DK103184, 1R21DK098531 and UL1 TR000040, to S.S.-C.; 2R01DK080099, to A.G.G.; 3U54DK104309, to A.G.G., C.L.M. and J.M.B.; R37HD033082, to V.E.P.; and 1R01DK105124 to K.K.) from the National Institutes of Health (NIH); a grant-in-aid (13GRNT14680075, to S.S.-C.) from the American Heart Association; a grant (RF-2010–2307403, to S.S.-C. and G.M.G.) from the Joint Italian Ministry of Health and NIH Young Investigators Finalized Research; a grant (to G.M.G.) from the Fondazione Malattie Renali nel Bambino; grants to D.E.B. and P.P. from the National Children’s Research Centre and the Irish Health Research Board (HRA-POR-2014–693); a grant (AAE07007KSA, to C.J.) from the GIS-Institut des Maladies Rares; by the Polish Ministry of Health (to A.M.K. and A.L.-B.); by the Polish Kidney Genetics Network (POLYGENES), the Polish Registry of Congenital Malformations (PRCM) and the NZOZ Center for Medical Genetics (GENESIS); by grants (to the Chronic Kidney Disease in Children Study) from the National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; by grants (U01DK66143, U01DK66174, U01DK082194, U01DK66116 and RO1DK082394) from the National Heart, Lung, and Blood Institute; and by the Paul Marks Scholar Award (to S.S.-C.); CNPq grant 460334/2014-0 and FAPEMIG grant PPM-005555-15 (to D.M.M., E.A.O. and A.C.S.-e.-S.); and a Kolff Postdoc Fellowship Abroad grant (15OKK95, to R.W.) from the Dutch Kidney Foundation. S.S.-C. is supported as the Florence Irving Assistant Professor of Medicine at Columbia University. We thank D.B. Goldstein for providing infrastructure for whole-exome sequencing at the Institute for Genomic Medicine (IGM) at Columbia University, and for critical review of the manuscript. Acknowledgments to the investigators who contributed of whole-exome sequencing data for 15,469 controls from the IGM warehouse can be found in the Supplementary Note.
Author information
Authors and Affiliations
Contributions
S.S.-C. directed the project. V.E.P., C.L.M., A.G.G. and S.S.-C. designed the project. M.V., R.W., A.P., Q.L., P.K., D.A.F., E.B., M.W., J.M., V.P.C., Y.-J.N., T.Y.L., D.A. and H.W. performed the experiments and/or data generation. M.G.S., M.G.D., J.M.D., P.P., D.E.B., S.L.F., B.A.W., C.J., D.M.M., E.A.O., A.C.S.-e.-S., F.H. and H.H. contributed array genotype data for CNV analyses. M.V., R.W., P.K., A.P., E.B., A.M., V.E.P., C.L.M. and S.S.-C. analyzed the data. K.K., J.M.B. and B.L. provided critical intellectual content for the design of the study. All other authors (A.M., M.B., C.K., A.V., S.S., B.H.K., M.M., J.Y.Z., P.L.W., E.L.H., A.C., G.P., L.G., V.M., G.M., M.G., D.C., C.I., F.S., J.A.E.v.W., M. Saraga, D.S., G.C., P.Z., D.D., K.Z., M.M., M.T., D.T., A.K., P.S., T.J., M.K.B.-K., R.P., M. Szczepanska., P.A., M.M.-W., G.K., A.S., M.Z., Z.G., V.J.L., V.T., I.P., L.A., L.M.R., J.M.C., S.A., P.C., F.L., W.N., G.M.G., A.L.-B., A.M.-K., C.S.W., N.W. and F.Z.) recruited cases and submitted clinical information for the study. M.V., R.W., V.E.P., C.L.M., A.G.G. and S.S.-C. wrote the draft of the manuscript. All authors critically revised the manuscript.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–12, Supplementary Tables 1–6 and 15, and Supplementary Note
Rights and permissions
About this article
Cite this article
Verbitsky, M., Westland, R., Perez, A. et al. The copy number variation landscape of congenital anomalies of the kidney and urinary tract. Nat Genet 51, 117–127 (2019). https://doi.org/10.1038/s41588-018-0281-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41588-018-0281-y
This article is cited by
-
Rare copy-number variants as modulators of common disease susceptibility
Genome Medicine (2024)
-
A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT
BMC Genomics (2024)
-
Contribution of genetic variants to congenital heart defects in both singleton and twin fetuses: a Chinese cohort study
Molecular Cytogenetics (2024)
-
Copy number variation analysis in 138 families with steroid-resistant nephrotic syndrome identifies causal homozygous deletions in PLCE1 and NPHS2 in two families
Pediatric Nephrology (2024)
-
Brain and spine malformations and neurodevelopmental disorders in a cohort of children with CAKUT
Pediatric Nephrology (2024)
