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Tytuł:
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RINT1 Bi-allelic Variations Cause Infantile-Onset Recurrent Acute Liver Failure and Skeletal Abnormalities.
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Autorzy:
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Cousin MA; Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA; Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Conboy E; Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA; Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA.
Wang JS; Department of Pediatrics, Jinshan Hospital, Fudan University, 201508 Shanghai, China; Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, 201102 Shanghai, China.
Lenz D; Department of General Pediatrics, Division of Neuropediatrics and Pediatric Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
Schwab TL; Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Williams M; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Abraham RS; Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH 43205, USA.
Barnett S; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
El-Youssef M; Department of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
Graham RP; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Gutierrez Sanchez LH; Department of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
Hasadsri L; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Hoffmann GF; Department of General Pediatrics, Division of Neuropediatrics and Pediatric Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
Hull NC; Department of Radiology, Division of Pediatric Radiology, Mayo Clinic, Rochester, MN 55905, USA.
Kopajtich R; Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany.
Kovacs-Nagy R; Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany.
Li JQ; Department of Pediatrics, Jinshan Hospital, Fudan University, 201508 Shanghai, China.
Marx-Berger D; Pediatric Nephrology, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland.
McLin V; Pediatric Gastroenterology Unit, University Hospitals Geneva, Rue Willy-Donzé 6, 1211 Geneva, Switzerland.
McNiven MA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
Mounajjed T; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Prokisch H; Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, 81675 Munich, Germany.
Rymen D; Department of Metabolic Diseases, University Children's Hospital Zurich, Zurich, Switzerland.
Schulze RJ; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
Staufner C; Department of General Pediatrics, Division of Neuropediatrics and Pediatric Metabolic Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.
Yang Y; Department of Pediatrics, Jinshan Hospital, Fudan University, 201508 Shanghai, China.
Clark KJ; Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Lanpher BC; Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA; Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: .
Klee EW; Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA; Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA; Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: .
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Źródło:
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American journal of human genetics [Am J Hum Genet] 2019 Jul 03; Vol. 105 (1), pp. 108-121. Date of Electronic Publication: 2019 Jun 13.
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Typ publikacji:
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Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: 2008- : [Cambridge, MA] : Cell Press
Original Publication: Baltimore, American Society of Human Genetics.
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MeSH Terms:
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Autophagy*
Mutation*
Bone Diseases, Developmental/*etiology
Cell Cycle Proteins/*genetics
Fibroblasts/*pathology
Liver Failure, Acute/*etiology
Age of Onset ; Alleles ; Amino Acid Sequence ; Bone Diseases, Developmental/metabolism ; Bone Diseases, Developmental/pathology ; Cell Cycle Proteins/metabolism ; Child ; Child, Preschool ; Female ; Fibroblasts/metabolism ; Golgi Apparatus/metabolism ; Golgi Apparatus/pathology ; Humans ; Infant ; Liver Failure, Acute/metabolism ; Liver Failure, Acute/pathology ; Male ; Pedigree ; Protein Transport ; Recurrence ; Sequence Homology
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References:
-
J Biol Chem. 2001 Mar 2;276(9):6105-11. (PMID: 11096100)
EMBO J. 2004 Mar 24;23(6):1267-78. (PMID: 15029241)
EMBO J. 2004 Aug 18;23(16):3216-26. (PMID: 15272311)
Mol Biol Cell. 2006 Jun;17(6):2780-8. (PMID: 16571679)
J Pediatr. 2006 May;148(5):652-658. (PMID: 16737880)
Mol Cell Biol. 2007 Jul;27(13):4905-16. (PMID: 17470549)
Mol Biol Cell. 2007 Oct;18(10):4129-42. (PMID: 17699596)
Mol Biol Cell. 2009 Jun;20(11):2639-49. (PMID: 19369418)
Bioinformatics. 2009 Jul 15;25(14):1754-60. (PMID: 19451168)
Bioinformatics. 2009 Aug 15;25(16):2078-9. (PMID: 19505943)
J Pediatr. 2009 Dec;155(6):801-806.e1. (PMID: 19643443)
Trends Cell Biol. 2010 May;20(5):257-68. (PMID: 20226673)
Mol Biol Cell. 2010 Jul 1;21(13):2270-84. (PMID: 20444982)
J Med Genet. 2010 Aug;47(8):538-48. (PMID: 20577004)
Genome Res. 2010 Sep;20(9):1297-303. (PMID: 20644199)
Curr Protoc Bioinformatics. 2010 Dec;Chapter 11:Unit 11.7. (PMID: 21154709)
Cell. 2011 Nov 11;147(4):728-41. (PMID: 22078875)
Genome Biol. 2013 Apr 25;14(4):R36. (PMID: 23618408)
Mol Biol Cell. 2013 Sep;24(18):2907-17. (PMID: 23885118)
Nat Cell Biol. 2013 Oct;15(10):1206-1219. (PMID: 24056303)
Bioinformatics. 2014 Jul 1;30(13):1920-2. (PMID: 24618464)
Cell Death Dis. 2014 Apr 17;5:e1179. (PMID: 24743734)
BMC Bioinformatics. 2014 Jun 27;15:224. (PMID: 24972667)
Cancer Discov. 2014 Jul;4(7):804-15. (PMID: 25050558)
Curr Protoc Bioinformatics. 2014 Sep 08;47:11.12.1-34. (PMID: 25199790)
Bioinformatics. 2015 Jan 15;31(2):166-9. (PMID: 25260700)
Am J Hum Genet. 2015 Jul 2;97(1):163-9. (PMID: 26073778)
Am J Med Genet A. 2015 Dec;167A(12):2902-12. (PMID: 26286438)
Cell Death Differ. 2016 Mar;23(3):454-68. (PMID: 26383973)
J Inherit Metab Dis. 2016 Jan;39(1):3-16. (PMID: 26541327)
Nature. 2015 Dec 10;528(7581):272-5. (PMID: 26595272)
Nat Commun. 2016 May 27;7:11600. (PMID: 27231034)
Nature. 2016 Aug 17;536(7616):285-91. (PMID: 27535533)
Breast Cancer Res Treat. 2016 Sep;159(2):385-92. (PMID: 27544226)
Hepatology. 2016 Dec;64(6):1994-2014. (PMID: 27637015)
Bone. 2017 Jan;94:65-74. (PMID: 27789416)
Hepatology. 2017 May;65(5):1655-1669. (PMID: 28027573)
PLoS One. 2017 Mar 6;12(3):e0172247. (PMID: 28264000)
Eur J Med Genet. 2017 Aug;60(8):426-432. (PMID: 28576691)
BMC Gastroenterol. 2017 Jun 19;17(1):77. (PMID: 28629372)
J Biol Chem. 2017 Aug 25;292(34):14050-14065. (PMID: 28710282)
J Clin Invest. 2017 Oct 2;127(10):3717-3729. (PMID: 28872463)
Ital J Pediatr. 2017 Sep 25;43(1):88. (PMID: 28946922)
Genet Med. 2018 Oct;20(10):1255-1265. (PMID: 29419818)
Elife. 2018 Mar 07;7:. (PMID: 29513218)
J Clin Immunol. 2018 Apr;38(3):307-319. (PMID: 29671115)
Mol Genet Metab. 2018 Jul;124(3):228-235. (PMID: 29759592)
Bone. 2018 Sep;114:125-136. (PMID: 29929043)
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Grant Information:
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P30 DK084567 United States DK NIDDK NIH HHS
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Contributed Indexing:
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Keywords: RINT1; autophagy; autosomal recessive; disorder of intracellular trafficking; recurrent acute liver failure; skeletal anomalies
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Substance Nomenclature:
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0 (Cell Cycle Proteins)
0 (RINT1 protein, human)
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Entry Date(s):
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Date Created: 20190618 Date Completed: 20200311 Latest Revision: 20200824
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Update Code:
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20240105
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PubMed Central ID:
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PMC6612521
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DOI:
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10.1016/j.ajhg.2019.05.011
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PMID:
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31204009
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Pediatric acute liver failure (ALF) is life threatening with genetic, immunologic, and environmental etiologies. Approximately half of all cases remain unexplained. Recurrent ALF (RALF) in infants describes repeated episodes of severe liver injury with recovery of hepatic function between crises. We describe bi-allelic RINT1 alterations as the cause of a multisystem disorder including RALF and skeletal abnormalities. Three unrelated individuals with RALF onset ≤3 years of age have splice alterations at the same position (c.1333+1G>A or G>T) in trans with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del) in RINT1. ALF episodes are concomitant with fever/infection and not all individuals have complete normalization of liver function testing between episodes. Liver biopsies revealed nonspecific liver damage including fibrosis, steatosis, or mild increases in Kupffer cells. Skeletal imaging revealed abnormalities affecting the vertebrae and pelvis. Dermal fibroblasts showed splice-variant mediated skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay. Fibroblasts also revealed decreased RINT1 protein, abnormal Golgi morphology, and impaired autophagic flux compared to control. RINT1 interacts with NBAS, recently implicated in RALF, and UVRAG, to facilitate Golgi-to-ER retrograde vesicle transport. During nutrient depletion or infection, Golgi-to-ER transport is suppressed and autophagy is promoted through UVRAG regulation by mTOR. Aberrant autophagy has been associated with the development of similar skeletal abnormalities and also with liver disease, suggesting that disruption of these RINT1 functions may explain the liver and skeletal findings. Clarifying the pathomechanism underlying this gene-disease relationship may inform therapeutic opportunities.
(Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
