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

Mir Reza Bekheirnia, Nasim Bekheirnia, Matthew N. Bainbridge, Shen Gu, Zeynep Hande Coban Akdemir, Tomek Gambin, Nicolette K. Janzen, Shalini N. Jhangiani, Donna M. Muzny, Mini Michael, Eileen D. Brewer, Ewa Elenberg, Arundhati S Kale, Alyssa A. Riley, Sarah J. Swartz, Daryl A. Scott, Yaping Yang, Poyyapakkam R. Srivaths, Scott E. Wenderfer, Joann Bodurtha & 16 others Carolyn D. Applegate, Milen Velinov, Angela Myers, Lior Borovik, William J. Craigen, Neil A. Hanchard, Jill A. Rosenfeld, Richard Alan Lewis, Edmond T. Gonzales, Richard A. Gibbs, John W. Belmont, David R. Roth, Christine Eng, Michael C. Braun, James R. Lupski, Dolores J. Lamb

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)412-420
Number of pages9
JournalGenetics in Medicine
Volume19
Issue number4
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Fingerprint

Exome
Nucleotides
Genes
Urinary Tract
Cakut
Databases
Phenotype

Keywords

  • CAKUT
  • FOXP1
  • HNF1B
  • PAX2
  • WES

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

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. / Bekheirnia, Mir Reza; Bekheirnia, Nasim; Bainbridge, Matthew N.; Gu, Shen; Akdemir, Zeynep Hande Coban; Gambin, Tomek; Janzen, Nicolette K.; Jhangiani, Shalini N.; Muzny, Donna M.; Michael, Mini; Brewer, Eileen D.; Elenberg, Ewa; Kale, Arundhati S; Riley, Alyssa A.; Swartz, Sarah J.; Scott, Daryl A.; Yang, Yaping; Srivaths, Poyyapakkam R.; Wenderfer, Scott E.; Bodurtha, Joann; Applegate, Carolyn D.; Velinov, Milen; Myers, Angela; Borovik, Lior; Craigen, William J.; Hanchard, Neil A.; Rosenfeld, Jill A.; Lewis, Richard Alan; Gonzales, Edmond T.; Gibbs, Richard A.; Belmont, John W.; Roth, David R.; Eng, Christine; Braun, Michael C.; Lupski, James R.; Lamb, Dolores J.

In: Genetics in Medicine, Vol. 19, No. 4, 01.04.2017, p. 412-420.

Research output: Contribution to journalArticle

Bekheirnia, MR, Bekheirnia, N, Bainbridge, MN, Gu, S, Akdemir, ZHC, Gambin, T, Janzen, NK, Jhangiani, SN, Muzny, DM, Michael, M, Brewer, ED, Elenberg, E, Kale, AS, Riley, AA, Swartz, SJ, Scott, DA, Yang, Y, Srivaths, PR, Wenderfer, SE, Bodurtha, J, Applegate, CD, Velinov, M, Myers, A, Borovik, L, Craigen, WJ, Hanchard, NA, Rosenfeld, JA, Lewis, RA, Gonzales, ET, Gibbs, RA, Belmont, JW, Roth, DR, Eng, C, Braun, MC, Lupski, JR & Lamb, DJ 2017, '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', Genetics in Medicine, vol. 19, no. 4, pp. 412-420. https://doi.org/10.1038/gim.2016.131
Bekheirnia, Mir Reza ; Bekheirnia, Nasim ; Bainbridge, Matthew N. ; Gu, Shen ; Akdemir, Zeynep Hande Coban ; Gambin, Tomek ; Janzen, Nicolette K. ; Jhangiani, Shalini N. ; Muzny, Donna M. ; Michael, Mini ; Brewer, Eileen D. ; Elenberg, Ewa ; Kale, Arundhati S ; Riley, Alyssa A. ; Swartz, Sarah J. ; Scott, Daryl A. ; Yang, Yaping ; Srivaths, Poyyapakkam R. ; Wenderfer, Scott E. ; Bodurtha, Joann ; Applegate, Carolyn D. ; Velinov, Milen ; Myers, Angela ; Borovik, Lior ; Craigen, William J. ; Hanchard, Neil A. ; Rosenfeld, Jill A. ; Lewis, Richard Alan ; Gonzales, Edmond T. ; Gibbs, Richard A. ; Belmont, John W. ; Roth, David R. ; Eng, Christine ; Braun, Michael C. ; Lupski, James R. ; Lamb, Dolores J. / 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. In: Genetics in Medicine. 2017 ; Vol. 19, No. 4. pp. 412-420.
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AU - Bekheirnia, Mir Reza

AU - Bekheirnia, Nasim

AU - Bainbridge, Matthew N.

AU - Gu, Shen

AU - Akdemir, Zeynep Hande Coban

AU - Gambin, Tomek

AU - Janzen, Nicolette K.

AU - Jhangiani, Shalini N.

AU - Muzny, Donna M.

AU - Michael, Mini

AU - Brewer, Eileen D.

AU - Elenberg, Ewa

AU - Kale, Arundhati S

AU - Riley, Alyssa A.

AU - Swartz, Sarah J.

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AU - Yang, Yaping

AU - Srivaths, Poyyapakkam R.

AU - Wenderfer, Scott E.

AU - Bodurtha, Joann

AU - Applegate, Carolyn D.

AU - Velinov, Milen

AU - Myers, Angela

AU - Borovik, Lior

AU - Craigen, William J.

AU - Hanchard, Neil A.

AU - Rosenfeld, Jill A.

AU - Lewis, Richard Alan

AU - Gonzales, Edmond T.

AU - Gibbs, Richard A.

AU - Belmont, John W.

AU - Roth, David R.

AU - Eng, Christine

AU - Braun, Michael C.

AU - Lupski, James R.

AU - Lamb, Dolores J.

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