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: 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).
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.Genet Med 19 4, 412-420.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas, USA.|Scott Department of Urology, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Mir Reza
authors.identifier: 0000-0002-2889-4558
authors.initials: MR
authors.lastname: Bekheirnia
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Nasim
authors.identifier: 0000-0003-3809-7760
authors.initials: N
authors.lastname: Bekheirnia
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Bainbridge
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Shen
authors.initials: S
authors.lastname: Gu
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Zeynep Hande
authors.initials: ZH
authors.lastname: Coban Akdemir
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Tomek
authors.identifier: 0000-0002-0941-4571
authors.initials: T
authors.lastname: Gambin
authors.affiliation: Scott Department of Urology, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Nicolette K
authors.initials: NK
authors.lastname: Janzen
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Shalini N
authors.initials: SN
authors.lastname: Jhangiani
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.affiliation: Texas Children's Hospital, Houston, Texas, USA.|Renal Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Mini
authors.identifier: 0000-0002-8562-1054
authors.initials: M
authors.lastname: Michael
authors.affiliation: Texas Children's Hospital, Houston, Texas, USA.|Renal Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Eileen D
authors.identifier: 0000-0002-7365-5986
authors.initials: ED
authors.lastname: Brewer
authors.affiliation: Texas Children's Hospital, Houston, Texas, USA.|Renal Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Ewa
authors.identifier: 0000-0003-3879-2536
authors.initials: E
authors.lastname: Elenberg
authors.affiliation: Texas Children's Hospital, Houston, Texas, USA.|Renal Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Arundhati S
authors.initials: AS
authors.lastname: Kale
authors.affiliation: Texas Children's Hospital, Houston, Texas, USA.|Renal Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Alyssa A
authors.identifier: 0000-0001-5113-0751
authors.initials: AA
authors.lastname: Riley
authors.affiliation: Texas Children's Hospital, Houston, Texas, USA.|Renal Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Sarah J
authors.identifier: 0000-0002-4409-3363
authors.initials: SJ
authors.lastname: Swartz
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Daryl A
authors.identifier: 0000-0003-1460-5169
authors.initials: DA
authors.lastname: Scott
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Texas Children's Hospital, Houston, Texas, USA.|Renal Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Poyyapakkam R
authors.initials: PR
authors.lastname: Srivaths
authors.affiliation: Texas Children's Hospital, Houston, Texas, USA.|Renal Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Scott E
authors.identifier: 0000-0002-8991-8277
authors.initials: SE
authors.lastname: Wenderfer
authors.affiliation: Johns Hopkins Children's Center, Institute of Genetic Medicine, Baltimore, Maryland, USA.
authors.forename: Joann
authors.identifier: 0000-0002-1667-5972
authors.initials: J
authors.lastname: Bodurtha
authors.affiliation: Johns Hopkins Children's Center, Institute of Genetic Medicine, Baltimore, Maryland, USA.
authors.forename: Carolyn D
authors.identifier: 0000-0002-9323-3887
authors.initials: CD
authors.lastname: Applegate
authors.affiliation: NYS Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA.
authors.forename: Milen
authors.initials: M
authors.lastname: Velinov
authors.affiliation: Sanford Children's Hospital, Sioux Falls, South Dakota, USA.
authors.forename: Angela
authors.identifier: 0000-0001-5074-0435
authors.initials: A
authors.lastname: Myers
authors.affiliation: Sanford Children's Hospital, Sioux Falls, South Dakota, USA.
authors.forename: Lior
authors.initials: L
authors.lastname: Borovik
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Hospital, Houston, Texas, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Craigen
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Hanchard
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jill A
authors.identifier: 0000-0001-5664-7987
authors.initials: JA
authors.lastname: Rosenfeld
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Hospital, Houston, Texas, USA.|Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Richard Alan
authors.identifier: 0000-0002-6644-6385
authors.initials: RA
authors.lastname: Lewis
authors.affiliation: Scott Department of Urology, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Hospital, Houston, Texas, USA.
authors.forename: Edmond T
authors.initials: ET
authors.lastname: Gonzales
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Hospital, Houston, Texas, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Belmont
authors.affiliation: Scott Department of Urology, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Hospital, Houston, Texas, USA.
authors.forename: David R
authors.identifier: 0000-0003-3800-8123
authors.initials: DR
authors.lastname: Roth
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Eng
authors.affiliation: Texas Children's Hospital, Houston, Texas, USA.|Renal Section, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Michael C
authors.identifier: 0000-0002-8039-450X
authors.initials: MC
authors.lastname: Braun
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Texas Children's Hospital, Houston, Texas, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.affiliation: Center for Reproductive Medicine, Baylor College of Medicine, Houston, Texas, USA.|Scott Department of Urology, Baylor College of Medicine, Houston, Texas, USA.|Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Dolores J
authors.identifier: 0000-0002-4389-5065
authors.initials: DJ
authors.lastname: Lamb
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D051762:PAX2 Transcription Factor / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014564:Urogenital Abnormalities / Q000175:diagnosis* / Q000235:genetics; D014718:Vesico-Ureteral Reflux / Q000175:diagnosis* / Q000235:genetics; D000073359:Exome Sequencing / Q000379:methods*; D055815:Young Adult
chemical_list: C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; C496495:HNF1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D012097:Repressor Proteins; D051539:Hepatocyte Nuclear Factor 1-beta; C104381:EYA1 protein, human; D017027:Protein Tyrosine Phosphatases