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Characterization of the renal phenotype in RMND1-related mitochondrial disease.

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  • معلومة اضافية
    • المصدر:
      Publisher: John Wiley & Sons Country of Publication: United States NLM ID: 101603758 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2324-9269 (Electronic) Linking ISSN: 23249269 NLM ISO Abbreviation: Mol Genet Genomic Med Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: [Hoboken, NJ] : John Wiley & Sons, [2013]-
    • الموضوع:
      Mutation*; Cell Cycle Proteins/*genetics ; Kidney Diseases/*genetics ; Mitochondrial Diseases/*genetics; Adolescent ; Child ; Female ; Humans ; Kidney Diseases/etiology ; Male ; Mitochondrial Diseases/complications ; Phenotype ; RNA Splice Sites
    • نبذة مختصرة :
      Background: The nuclear encoded gene RMND1 (Required for Meiotic Nuclear Division 1 homolog) has recently been linked to RMND1-related mitochondrial disease (RRMD). This autosomal recessive condition characteristically presents with an infantile-onset multisystem disease characterized by severe hypotonia, global developmental delay, failure to thrive, sensorineural hearing loss, and lactic acidosis. Renal disease, however, appears to be one of the more prominent features of RRMD, affecting patients at significantly higher numbers compared to other mitochondrial diseases. We report the clinical, histological, and molecular findings of four RRMD patients across three academic institutions with a focus on the renal manifestations.
      Methods: Four patients were identified for the purpose of this study, all of whom had molecular confirmation at the time of inclusion, which included the common pathogenic variant c.713A>G (p.N238S) as well as the three rare variants: c.485delC (p.P162fs), c.533C>T (p.T178M), and c.1317 + 1G>C splice donor variant. Medical history and laboratory findings were collected from the medical records and medical providers.
      Results: In this study, all four patients developed renal disease characterized as tubulopathy (3/4), renal tubular acidosis (2/4), interstitial nephritis (1/4), and/or end-stage renal disease (4/4) necessitating renal transplantation (2/4). Histological evaluation of renal biopsy specimens revealed generalized tubular atrophy and on electron microscopy, abundant mitochondria with pleomorphism and abnormal cristae.
      Conclusion: Our experience with RRMD demonstrates a specific pattern of renal disease manifestations and clinical course. Patients are unlikely to respond to traditional chronic kidney disease (CKD) treatments, making early diagnosis and consideration of renal transplantation paramount to the management of RRMD.
      (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)
    • References:
      J Clin Invest. 2013 Dec;123(12):5179-89. (PMID: 24270420)
      Mol Genet Genomic Med. 2019 Dec;7(12):e973. (PMID: 31568715)
      J Am Soc Nephrol. 2019 Feb 8;:. (PMID: 30737270)
      Mol Genet Metab. 2016 Jul;118(3):178-84. (PMID: 27312126)
      Pediatr Dev Pathol. 2005 Nov-Dec;8(6):710-7. (PMID: 16328667)
      Intern Med. 2001 Jul;40(7):662-5. (PMID: 11506313)
      Adv Exp Med Biol. 2017;982:529-551. (PMID: 28551805)
      Genet Med. 2015 May;17(5):405-24. (PMID: 25741868)
      Eur J Hum Genet. 2015 Oct;23(10):1301-7. (PMID: 25604853)
      Am J Hum Genet. 2012 Oct 5;91(4):729-36. (PMID: 23022099)
      Pediatr Neurol. 2017 Jan;66:59-62. (PMID: 27843092)
      Am J Med Genet A. 2016 Jan;170A(1):142-7. (PMID: 26395190)
      Am J Hum Genet. 2012 Oct 5;91(4):737-43. (PMID: 23022098)
      J Am Soc Nephrol. 2003 Dec;14(12):2995-3007. (PMID: 14638899)
      Clin Nephrol. 2013 Dec;80(6):456-63. (PMID: 22909780)
      Am J Surg Pathol. 2010 Feb;34(2):262-70. (PMID: 20090504)
      BMC Res Notes. 2016 Jun 27;9:325. (PMID: 27350610)
      Biomed Rep. 2017 May;6(5):487-494. (PMID: 28515908)
      Am J Physiol Renal Physiol. 2014 Feb 15;306(4):F367-78. (PMID: 24305473)
      J Med Genet. 2016 Nov;53(11):768-775. (PMID: 27412952)
      Am J Physiol Renal Physiol. 2008 Nov;295(5):F1535-44. (PMID: 18784258)
      Pediatr Nephrol. 2005 Sep;20(9):1299-305. (PMID: 15977024)
    • Grant Information:
      K12 DK083014 United States DK NIDDK NIH HHS; R01 DK078121 United States DK NIDDK NIH HHS
    • Contributed Indexing:
      Keywords: RMND1; Mitochondrial disease; chronic kidney disease; renal transplantation
    • الرقم المعرف:
      0 (Cell Cycle Proteins)
      0 (RMND1 protein, human)
      0 (RNA Splice Sites)
    • الموضوع:
      Date Created: 20191001 Date Completed: 20200619 Latest Revision: 20230929
    • الموضوع:
      20250114
    • الرقم المعرف:
      PMC6900359
    • الرقم المعرف:
      10.1002/mgg3.973
    • الرقم المعرف:
      31568715