Mutations in Keops-Complex Genes Cause Nephritic Syndrome With Primary Microcephaly

Mutations in Keops-Complex Genes Cause Nephritic Syndrome With Primary Microcephaly Publisher Pubmed

Braun DA¹ ; Rao J¹ ; Mollet G^{2, 3} ; Schapiro D¹ ; Daugeron MC⁴ ; Tan W¹ ; Gribouval O^{2, 3} ; Boyer O^{2, 3, 5} ; Revy P^{3, 6} ; Jobstschwan T¹ ; Schmidt JM¹ ; Lawson JA¹ ; Schanze D⁷ ; Ashraf S¹ Show All Authors

Braun DA¹
Rao J¹
Mollet G^{2, 3}
Schapiro D¹
Daugeron MC⁴
Tan W¹
Gribouval O^{2, 3}
Boyer O^{2, 3, 5}
Revy P^{3, 6}
Jobstschwan T¹
Schmidt JM¹
Lawson JA¹
Schanze D⁷
Ashraf S¹
Ullmann JFP^{8, 9}
Hoogstraten CA¹
Boddaert N^{3, 10, 11}
Collinet B^{4, 12, 13}
Martin G^{2, 3}
Liger D⁴
Lovric S¹
Furlano M^{2, 3, 14}
Guerrera IC¹⁵
Sanchezferras O¹⁶
Hu JF¹⁷
Boschat AC¹⁸
Sanquer S^{19, 20}
Menten B²¹
Vergult S²¹
De Rocker N²¹
Airik M¹
Hermle T¹
Shril S¹
Widmeier E^{1, 22}
Yung Gee H^{1, 23}
Choi WI¹
Sadowski CE¹
Pabst WL¹
Warejko JK¹
Daga A¹
Basta T⁴
Matejas V²⁴
Scharmann K^{25, 26}
Kienast SD^{25, 26}
Behnam B^{27, 28}
Beeson B²⁹
Begtrup A³⁰
Bruce M²⁹
Chng GS³¹
Lin SP^{32, 33}
Chang JH³⁴
Chen CH³⁵
Cho MT³⁰
Gaffney PM³⁶
Gipson PE³⁷
Hsu CH³⁴
Kari JA³⁸
Ke YY³⁵
Kiralyborri C³⁹
Lai WM⁴⁰
Lemyre E⁴¹
Littlejohn RO^{42, 43}
Masri A⁴⁴
Moghtaderi M⁴⁵
Nakamura K⁴⁶
Ozaltin F^{47, 48, 49}
Praet M⁵⁰
Prasad C⁵¹
Prytula A⁵²
Roeder ER^{42, 43}
Rump P⁵³
Schnur RE³⁰
Shiihara T⁴⁶
Sinha MD⁵⁴
Soliman NA^{55, 56}
Soulami K⁵⁷
Sweetser DA⁵⁸
Tsai WH⁵⁹
Tsai JD^{33, 34, 60, 61}
Topaloglu R⁴⁷
Vester U⁶²
Viskochil DH⁶³
Vatanavicharn N⁶⁴
Waxler JL⁵⁸
Wierenga KJ⁶⁵
Wolf MTF⁶⁶
Wong SN⁶⁷
Leidel SA^{25, 26, 68}
Truglio G⁸
Dedon PC^{69, 70}
Poduri A^{8, 9}
Mane S⁷¹
Lifton RP^{71, 72}
Bouchard M¹⁶
Kannu P⁷³
Chitayat D⁷³
Magen D⁷⁴
Callewaert B²¹
Van Tilbeurgh H⁴
Zenker M⁷
Antignac C^{2, 3, 75}
Hildebrandt F¹

Show Affiliations

1. Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States
2. Laboratory of Hereditary Kidney Diseases, INSERM UMR1163, Imagine Institute, Paris, France
3. Universite Paris Descartes-Sorbonne Paris Cite, Imagine Institute, Paris, France
4. Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Universite Paris-Sud, Universite Paris-Saclay, Gif-sur-Yvette, France
5. Department of Pediatric Nephrology, Necker Hospital, Assistance Publique-Hopitaux de Paris, Paris, France
6. INSERM, U1163, Imagine Institute, Laboratory of Genome Dynamics in the Immune System, Paris, France
7. Institute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany
8. Epilepsy Genetics Program and F.M Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Boston, MA, United States
9. Department of Neurology, Harvard Medical School, Boston, MA, United States
10. INSERM U1000, Paris, France
11. Department of Pediatric Radiology, Necker Hospital, Assistance Publique-Hopitaux de Paris, Paris, France
12. Sorbonne Universites UPMC, UFR 927, Sciences de la Vie, Paris, France
13. Institut de Mineralogie, De Physique des Materiaux et de Cosmochimie UMR 7590, Sorbonne Universites, UPMC, Universite Paris 06, Paris, France
14. Nephrology Department, Fundacio Puigvert, IIB Sant Pau, Universitat Autonoma de Barcelona and REDINREN, Barcelona, Spain
15. Proteomics Platform 3P5-Necker, Universite Paris Descartes-Structure Federative de Recherche Necker, INSERM US24/CNRS UMS3633, Paris, France
16. Goodman Cancer Research Centre and Department of Biochemistry, McGill University, Montreal, QC, Canada
17. Departments of Chemistry and Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States
18. Mass Spectrometry Platform, Imagine Institute, Paris, France
19. Department of Metabolomic and Proteomic Biochemistry, Necker Hospital, Assistance Publique-Hopitaux de Paris, Paris, France
20. INSERM UMR-S1124, Paris Descartes-Sorbonne Paris Cite University, Paris, France
21. Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
22. Department of Medicine, Renal Division, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
23. Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, South Korea
24. Institute of Human Genetics, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen, Germany
25. Max Planck Institute for Molecular Biomedicine, Muenster, Germany
26. Cells-in-Motion Cluster of Excellence, University of Muenster, Muenster, Germany
27. Department of Medical Genetics and Molecular Biology, Iran University of Medical Sciences (IUMS), Tehran, Iran
28. Medical Genetics Branch, National Human Genome Research Institute (NHGRI), Undiagnosed Diseases Program, Bethesda, MD, United States
29. Department of Diagnostic Imaging, Princess Margaret and King Edward Memorial Hospitals, Perth, WA, Australia
30. GeneDx, Gaithersburg, MD, United States
31. Department of Genetics, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia
32. Department of Pediatric Genetics, MacKay Children's Hospital, Taipei, Taiwan
33. Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
34. Department of Pediatrics, MacKay Children's Hospital, Taipei, Taiwan
35. Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan
36. Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States
37. Internal Medicine and Pediatrics Divisions of Adult and Pediatric Nephrology, University of Michigan, Ann Arbor, MI, United States
38. Pediatric Nephrology Center of Excellence and Pediatric Department, King Abdulaziz University, Jeddah, Saudi Arabia
39. Genetic Services of Western Australia, Princess Margaret Hospital for Children, King Edward Memorial Hospital for Women, Subiaco, WA, Australia
40. Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong, Hong Kong
41. Service de Genetique Medicale, Departement de Pediatrie, Universite de Montreal, Montreal 1, QC, Canada
42. Department of Pediatrics, Baylor College of Medicine, San Antonio, TX, United States
43. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States
44. Department of Pediatrics, Faculty of Medicine, University of Jordan, Amman, Jordan
45. Chronic Kidney Disease Research Center, Tehran University of Medical Science, Tehran, Iran
46. Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan
47. Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Hacettepe University, Ankara, Turkey
48. Nephrogenetics Laboratory, Hacettepe University Faculty of Medicine, Hacettepe University, Ankara, Turkey
49. Hacettepe University Center for Biobanking and Genomics, Hacettepe University, Ankara, Turkey
50. Department of Pathology, Ghent University Hospital, Ghent, Belgium
51. Department of Genetics Metabolism and Pediatrics, Western University, London Health Sciences Centre, London, ON, Canada
52. Department of Pediatrics, Ghent University Hospital, Ghent, Belgium
53. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
54. Department of Paediatric Nephrology, Kings College London, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
55. Department of Pediatrics, Center of Pediatric Nephrology and Transplantation, Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt
56. Egyptian Group for Orphan Renal Diseases, Cairo, Egypt
57. Department of Nephrology, Ibn Rochd University Hospital, Casablanca, Morocco
58. Division of Medical Genetics, Massachusetts General Hospital for Children, Boston, MA, United States
59. Division of Genetics and Metabolism, Department of Pediatrics, Chi Mei Medical Center, Tainan, Taiwan
60. Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan
61. Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
62. Department of Pediatrics II, University Hospital Essen, Essen, Germany
63. Department of Pediatrics, Division of Medical Genetics, University of Utah School of Medicine, Salt Lake City, UT, United States
64. Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
65. Department of Pediatrics, Oklahoma University Health Sciences Center (OUHSC), Oklahoma City, OK, United States
66. Division of Pediatric Nephrology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States
67. Department of Pediatrics and Adolescent Medicine, Tuen Mun Hospital, Tuen Mun, Hong Kong
68. Medical Faculty, University of Muenster, Muenster, Germany
69. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States
70. Singapore-MIT Alliance for Research and Technology, Infectious Disease IRG, Singapore
71. Department of Genetics, Yale University School of Medicine, New Haven, CT, United States
72. Laboratory of Human Genetics and Genomics, Rockefeller University, New York, NY, United States
73. Department of Pediatrics, Division of Clinical and Metabolic Genetics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
74. Pediatric Nephrology Institute, Rambam Health Care Campus, Haifa, Israel
75. Department of Genetics, Necker Hospital, Assistance Publique-Hopitaux de Paris, Paris, France

Source: Nature Genetics Published:2017

Abstract

Galloway-Mowat syndrome (GAMOS) is an autosomalrecessive disease characterized by the combination of earlyonset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.

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Style	Citing Format
MLA	Braun DA, et al.. "Mutations in Keops-Complex Genes Cause Nephritic Syndrome With Primary Microcephaly." Nature Genetics, vol. 49, no. 10, 2017, pp. 1529-1538.
APA	Braun DA, Rao J, Mollet G, Schapiro D, Daugeron MC, Tan W, Gribouval O, Boyer O, Revy P, Jobstschwan T, Schmidt JM, Lawson JA, Schanze D, Ashraf S, Ullmann JFP, Hoogstraten CA, Boddaert N, Collinet B, Martin G, ... Hildebrandt F (2017). Mutations in Keops-Complex Genes Cause Nephritic Syndrome With Primary Microcephaly. Nature Genetics, 49(10), 1529-1538.
Chicago	Braun DA, Rao J, Mollet G, Schapiro D, Daugeron MC, Tan W, Gribouval O, et al.. "Mutations in Keops-Complex Genes Cause Nephritic Syndrome With Primary Microcephaly." Nature Genetics 49, no. 10 (2017): 1529-1538.
Harvard	Braun DA et al. (2017) 'Mutations in Keops-Complex Genes Cause Nephritic Syndrome With Primary Microcephaly', Nature Genetics, 49(10), pp. 1529-1538.
Vancouver	Braun DA, Rao J, Mollet G, Schapiro D, Daugeron MC, Tan W, et al.. Mutations in Keops-Complex Genes Cause Nephritic Syndrome With Primary Microcephaly. Nature Genetics. 2017;49(10):1529-1538.
BibTex	@article{ author = {Braun DA and Rao J and Mollet G and Schapiro D and Daugeron MC and Tan W and Gribouval O and Boyer O and Revy P and Jobstschwan T and Schmidt JM and Lawson JA and Schanze D and Ashraf S and Ullmann JFP and Hoogstraten CA and Boddaert N and Collinet B and Martin G and Liger D and Lovric S and Furlano M and Guerrera IC and Sanchezferras O and Hu JF and Boschat AC and Sanquer S and Menten B and Vergult S and De Rocker N and Airik M and Hermle T and Shril S and Widmeier E and Yung Gee H and Choi WI and Sadowski CE and Pabst WL and Warejko JK and Daga A and Basta T and Matejas V and Scharmann K and Kienast SD and Behnam B and Beeson B and Begtrup A and Bruce M and Chng GS and Lin SP and Chang JH and Chen CH and Cho MT and Gaffney PM and Gipson PE and Hsu CH and Kari JA and Ke YY and Kiralyborri C and Lai WM and Lemyre E and Littlejohn RO and Masri A and Moghtaderi M and Nakamura K and Ozaltin F and Praet M and Prasad C and Prytula A and Roeder ER and Rump P and Schnur RE and Shiihara T and Sinha MD and Soliman NA and Soulami K and Sweetser DA and Tsai WH and Tsai JD and Topaloglu R and Vester U and Viskochil DH and Vatanavicharn N and Waxler JL and Wierenga KJ and Wolf MTF and Wong SN and Leidel SA and Truglio G and Dedon PC and Poduri A and Mane S and Lifton RP and Bouchard M and Kannu P and Chitayat D and Magen D and Callewaert B and Van Tilbeurgh H and Zenker M and Antignac C and Hildebrandt F}, title = {Mutations in Keops-Complex Genes Cause Nephritic Syndrome With Primary Microcephaly}, journal = {Nature Genetics}, volume = {49}, number = {10}, pages = {1529-1538}, year = {2017} }
RIS	TY - JOUR AU - Braun DA AU - Rao J AU - Mollet G AU - Schapiro D AU - Daugeron MC AU - Tan W AU - Gribouval O AU - Boyer O AU - Revy P AU - Jobstschwan T AU - Schmidt JM AU - Lawson JA AU - Schanze D AU - Ashraf S AU - Ullmann JFP AU - Hoogstraten CA AU - Boddaert N AU - Collinet B AU - Martin G AU - Liger D AU - Lovric S AU - Furlano M AU - Guerrera IC AU - Sanchezferras O AU - Hu JF AU - Boschat AC AU - Sanquer S AU - Menten B AU - Vergult S AU - De Rocker N AU - Airik M AU - Hermle T AU - Shril S AU - Widmeier E AU - Yung Gee H AU - Choi WI AU - Sadowski CE AU - Pabst WL AU - Warejko JK AU - Daga A AU - Basta T AU - Matejas V AU - Scharmann K AU - Kienast SD AU - Behnam B AU - Beeson B AU - Begtrup A AU - Bruce M AU - Chng GS AU - Lin SP AU - Chang JH AU - Chen CH AU - Cho MT AU - Gaffney PM AU - Gipson PE AU - Hsu CH AU - Kari JA AU - Ke YY AU - Kiralyborri C AU - Lai WM AU - Lemyre E AU - Littlejohn RO AU - Masri A AU - Moghtaderi M AU - Nakamura K AU - Ozaltin F AU - Praet M AU - Prasad C AU - Prytula A AU - Roeder ER AU - Rump P AU - Schnur RE AU - Shiihara T AU - Sinha MD AU - Soliman NA AU - Soulami K AU - Sweetser DA AU - Tsai WH AU - Tsai JD AU - Topaloglu R AU - Vester U AU - Viskochil DH AU - Vatanavicharn N AU - Waxler JL AU - Wierenga KJ AU - Wolf MTF AU - Wong SN AU - Leidel SA AU - Truglio G AU - Dedon PC AU - Poduri A AU - Mane S AU - Lifton RP AU - Bouchard M AU - Kannu P AU - Chitayat D AU - Magen D AU - Callewaert B AU - Van Tilbeurgh H AU - Zenker M AU - Antignac C AU - Hildebrandt F TI - Mutations in Keops-Complex Genes Cause Nephritic Syndrome With Primary Microcephaly JO - Nature Genetics VL - 49 IS - 10 SP - 1529 EP - 1538 PY - 2017 ER -

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