@article{c24dd62c5061468f8830fae0c8bd3ed3,
title = "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",
abstract = "Purpose: To investigate the utility of whole-exome sequencing (WES) to define a molecular diagnosis for patients clinically diagnosed with congenital anomalies of kidney and urinary tract (CAKUT). Methods: WES was performed in 62 families with CAKUT. WES data were analyzed for single-nucleotide variants (SNVs) in 35 known CAKUT genes, putatively deleterious sequence changes in new candidate genes, and potentially disease-associated copy-number variants (CNVs). Results: In approximately 5% of families, pathogenic SNVs were identified in PAX2, HNF1B, and EYA1. Observed phenotypes in these families expand the current understanding about the role of these genes in CAKUT. Four pathogenic CNVs were also identified using two CNV detection tools. In addition, we found one deleterious de novo SNV in FOXP1 among the 62 families with CAKUT. The clinical database of the Baylor Miraca Genetics laboratory was queried and seven additional unrelated individuals with novel de novo SNVs in FOXP1 were identified. Six of these eight individuals with FOXP1 SNVs have syndromic urinary tract defects, implicating this gene in urinary tract development. Conclusion: We conclude that WES can be used to identify molecular etiology (SNVs, CNVs) in a subset of individuals with CAKUT. WES can also help identify novel CAKUT genes.",
keywords = "CAKUT, FOXP1, HNF1B, PAX2, WES",
author = "Bekheirnia, {Mir Reza} and Nasim Bekheirnia and Bainbridge, {Matthew N.} and Shen Gu and Akdemir, {Zeynep Hande Coban} and Tomek Gambin and Janzen, {Nicolette K.} and Jhangiani, {Shalini N.} and Muzny, {Donna M.} and Mini Michael and Brewer, {Eileen D.} and Ewa Elenberg and Kale, {Arundhati S.} and Riley, {Alyssa A.} and Swartz, {Sarah J.} and Scott, {Daryl A.} and Yaping Yang and Srivaths, {Poyyapakkam R.} and Wenderfer, {Scott E.} and Joann Bodurtha and Applegate, {Carolyn D.} and Milen Velinov and Angela Myers and Lior Borovik and Craigen, {William J.} and Hanchard, {Neil A.} and Rosenfeld, {Jill A.} and Lewis, {Richard Alan} and Gonzales, {Edmond T.} and Gibbs, {Richard A.} and Belmont, {John W.} and Roth, {David R.} and Christine Eng and Braun, {Michael C.} and Lupski, {James R.} and Lamb, {Dolores J.}",
note = "Funding Information: This study was supported in part by K12 DK083014 Multidisciplinary K12 Urologic Research Career Development Program and R01 DK078121 from the National Institute of Diabetes and Digestive and Kidney Diseases awarded to D.J.L. This work was funded in part by grant R01 NS058529 (JRL) from the National Institute of Neurological Disorders and Stroke and U54 HG006542 from the National Human Genome Research Institute/National Heart Lung and Blood Institute to the Baylor Hopkins Center for Mendelian Genomics. Supported in part also by a National Institutes of Human Genome Research (NHGRI) (U54HG003273) awarded to R.A.G. R.A.L. is a Senior Scientific Investigator of Research to Prevent Blindness whose unrestricted funding supported part of this study.",
year = "2017",
month = apr,
day = "1",
doi = "10.1038/gim.2016.131",
language = "English (US)",
volume = "19",
pages = "412--420",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Elsevier B.V.",
number = "4",
}