Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association

Pawaree Saisawat, Stefan Kohl, Alina C. Hilger, Daw Yang Hwang, Heon Yung Gee, Gabriel C. Dworschak, Velibor Tasic, Tracie Pennimpede, Sivakumar Natarajan, Ethan Sperry, Danilo S. Matassa, Nataša Stajić, Radovan Bogdanovic, Ivo De Blaauw, Carlo L.M. Marcelis, Charlotte H.W. Wijers, Enrika Bartels, Eberhard Schmiedeke, Dominik Schmidt, Stefanie MärzheuserSabine Grasshoff-Derr, Stefan Holland-Cunz, Michael Ludwig, Markus M. Nöthen, Markus Draaken, Erwin Brosens, Hugo Heij, Dick Tibboel, Bernhard G. Herrmann, Benjamin D. Solomon, Annelies De Klein, Iris A.L.M. Van Rooij, Franca Esposito, Heiko M. Reutter, Friedhelm Hildebrandt

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60% of the cases. By homozygosity mapping and whole-exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat-shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henle's loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or VACTERL association with CAKUT.

Original languageEnglish
Pages (from-to)1310-1317
Number of pages8
JournalKidney International
Volume85
Issue number6
DOIs
Publication statusPublished - 2014 Jun

Fingerprint

TNF Receptor-Associated Factor 1
Exome
Urinary Tract
Kidney
Mutation
Loop of Henle
HSP90 Heat-Shock Proteins
Endoplasmic Reticulum Stress
VACTERL association
Multiplex Polymerase Chain Reaction
Chronic Renal Insufficiency
Chronic Kidney Failure
Epithelium

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Saisawat, P., Kohl, S., Hilger, A. C., Hwang, D. Y., Yung Gee, H., Dworschak, G. C., ... Hildebrandt, F. (2014). Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association. Kidney International, 85(6), 1310-1317. https://doi.org/10.1038/ki.2013.417
Saisawat, Pawaree ; Kohl, Stefan ; Hilger, Alina C. ; Hwang, Daw Yang ; Yung Gee, Heon ; Dworschak, Gabriel C. ; Tasic, Velibor ; Pennimpede, Tracie ; Natarajan, Sivakumar ; Sperry, Ethan ; Matassa, Danilo S. ; Stajić, Nataša ; Bogdanovic, Radovan ; De Blaauw, Ivo ; Marcelis, Carlo L.M. ; Wijers, Charlotte H.W. ; Bartels, Enrika ; Schmiedeke, Eberhard ; Schmidt, Dominik ; Märzheuser, Stefanie ; Grasshoff-Derr, Sabine ; Holland-Cunz, Stefan ; Ludwig, Michael ; Nöthen, Markus M. ; Draaken, Markus ; Brosens, Erwin ; Heij, Hugo ; Tibboel, Dick ; Herrmann, Bernhard G. ; Solomon, Benjamin D. ; De Klein, Annelies ; Van Rooij, Iris A.L.M. ; Esposito, Franca ; Reutter, Heiko M. ; Hildebrandt, Friedhelm. / Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association. In: Kidney International. 2014 ; Vol. 85, No. 6. pp. 1310-1317.
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abstract = "Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60{\%} of the cases. By homozygosity mapping and whole-exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat-shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henle's loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or VACTERL association with CAKUT.",
author = "Pawaree Saisawat and Stefan Kohl and Hilger, {Alina C.} and Hwang, {Daw Yang} and {Yung Gee}, Heon and Dworschak, {Gabriel C.} and Velibor Tasic and Tracie Pennimpede and Sivakumar Natarajan and Ethan Sperry and Matassa, {Danilo S.} and Nataša Stajić and Radovan Bogdanovic and {De Blaauw}, Ivo and Marcelis, {Carlo L.M.} and Wijers, {Charlotte H.W.} and Enrika Bartels and Eberhard Schmiedeke and Dominik Schmidt and Stefanie M{\"a}rzheuser and Sabine Grasshoff-Derr and Stefan Holland-Cunz and Michael Ludwig and N{\"o}then, {Markus M.} and Markus Draaken and Erwin Brosens and Hugo Heij and Dick Tibboel and Herrmann, {Bernhard G.} and Solomon, {Benjamin D.} and {De Klein}, Annelies and {Van Rooij}, {Iris A.L.M.} and Franca Esposito and Reutter, {Heiko M.} and Friedhelm Hildebrandt",
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Saisawat, P, Kohl, S, Hilger, AC, Hwang, DY, Yung Gee, H, Dworschak, GC, Tasic, V, Pennimpede, T, Natarajan, S, Sperry, E, Matassa, DS, Stajić, N, Bogdanovic, R, De Blaauw, I, Marcelis, CLM, Wijers, CHW, Bartels, E, Schmiedeke, E, Schmidt, D, Märzheuser, S, Grasshoff-Derr, S, Holland-Cunz, S, Ludwig, M, Nöthen, MM, Draaken, M, Brosens, E, Heij, H, Tibboel, D, Herrmann, BG, Solomon, BD, De Klein, A, Van Rooij, IALM, Esposito, F, Reutter, HM & Hildebrandt, F 2014, 'Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association', Kidney International, vol. 85, no. 6, pp. 1310-1317. https://doi.org/10.1038/ki.2013.417

Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association. / Saisawat, Pawaree; Kohl, Stefan; Hilger, Alina C.; Hwang, Daw Yang; Yung Gee, Heon; Dworschak, Gabriel C.; Tasic, Velibor; Pennimpede, Tracie; Natarajan, Sivakumar; Sperry, Ethan; Matassa, Danilo S.; Stajić, Nataša; Bogdanovic, Radovan; De Blaauw, Ivo; Marcelis, Carlo L.M.; Wijers, Charlotte H.W.; Bartels, Enrika; Schmiedeke, Eberhard; Schmidt, Dominik; Märzheuser, Stefanie; Grasshoff-Derr, Sabine; Holland-Cunz, Stefan; Ludwig, Michael; Nöthen, Markus M.; Draaken, Markus; Brosens, Erwin; Heij, Hugo; Tibboel, Dick; Herrmann, Bernhard G.; Solomon, Benjamin D.; De Klein, Annelies; Van Rooij, Iris A.L.M.; Esposito, Franca; Reutter, Heiko M.; Hildebrandt, Friedhelm.

In: Kidney International, Vol. 85, No. 6, 06.2014, p. 1310-1317.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association

AU - Saisawat, Pawaree

AU - Kohl, Stefan

AU - Hilger, Alina C.

AU - Hwang, Daw Yang

AU - Yung Gee, Heon

AU - Dworschak, Gabriel C.

AU - Tasic, Velibor

AU - Pennimpede, Tracie

AU - Natarajan, Sivakumar

AU - Sperry, Ethan

AU - Matassa, Danilo S.

AU - Stajić, Nataša

AU - Bogdanovic, Radovan

AU - De Blaauw, Ivo

AU - Marcelis, Carlo L.M.

AU - Wijers, Charlotte H.W.

AU - Bartels, Enrika

AU - Schmiedeke, Eberhard

AU - Schmidt, Dominik

AU - Märzheuser, Stefanie

AU - Grasshoff-Derr, Sabine

AU - Holland-Cunz, Stefan

AU - Ludwig, Michael

AU - Nöthen, Markus M.

AU - Draaken, Markus

AU - Brosens, Erwin

AU - Heij, Hugo

AU - Tibboel, Dick

AU - Herrmann, Bernhard G.

AU - Solomon, Benjamin D.

AU - De Klein, Annelies

AU - Van Rooij, Iris A.L.M.

AU - Esposito, Franca

AU - Reutter, Heiko M.

AU - Hildebrandt, Friedhelm

PY - 2014/6

Y1 - 2014/6

N2 - Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60% of the cases. By homozygosity mapping and whole-exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat-shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henle's loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or VACTERL association with CAKUT.

AB - Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60% of the cases. By homozygosity mapping and whole-exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat-shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henle's loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or VACTERL association with CAKUT.

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