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Diverse phenotype in patients with complex I deficiency due to mutations in NDUFB11.

Authors
  • Reinson, Karit1
  • Kovacs-Nagy, Reka2
  • Õiglane-Shlik, Eve3
  • Pajusalu, Sander4
  • Nõukas, Margit5
  • Wintjes, Liesbeth T6
  • van den Brandt, Frans C A6
  • Brink, Maaike6
  • Acker, Till7
  • Ahting, Uwe8
  • Hahn, Andreas9
  • Schänzer, Anne7
  • Haack, Tobias B10
  • Rodenburg, Richard J11
  • Õunap, Katrin12
  • 1 Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia; Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia. , (Estonia)
  • 2 Institute of Human Genetics, Technische Universität München, Munich, Germany; Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University Budapest, Hungary. , (Germany)
  • 3 Department of Pediatrics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia; Children's Clinic, Tartu University Hospital, Tartu, Estonia. , (Estonia)
  • 4 Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia. , (Estonia)
  • 5 Estonian Genome Center, University of Tartu, Tartu, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. , (Estonia)
  • 6 Radboud Center for Mitochondrial Medicine, Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. , (Netherlands)
  • 7 Institute of Neuropathology, JL University of Giessen, Giessen, Germany. , (Germany)
  • 8 Institute of Human Genetics, Technische Universität München, Munich, Germany. , (Germany)
  • 9 Department of Child Neurology, JL University of Giessen, Giessen, Germany. , (Germany)
  • 10 Institute of Human Genetics, Technische Universität München, Munich, Germany; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tuebingen, Germany. , (Germany)
  • 11 Radboud Center for Mitochondrial Medicine, Translational Metabolic Laboratory, Department of Pediatrics, Radboud University Medical Center, Nijmegen, the Netherlands. , (Netherlands)
  • 12 Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia; Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia. Electronic address: [email protected] , (Estonia)
Type
Published Article
Journal
European journal of medical genetics
Publication Date
Nov 01, 2019
Volume
62
Issue
11
Pages
103572–103572
Identifiers
DOI: 10.1016/j.ejmg.2018.11.006
PMID: 30423443
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Mitochondrial complex I deficiency is the most frequent mitochondrial disorder presenting in childhood and the mutational spectrum is highly heterogeneous. The NDUFB11 gene is one of the recently identified genes, which is located in the short arm of the X-chromosome. Here we report clinical, biochemical, functional and genetic findings of two male patients with lactic acidosis, hypertrophic cardiomyopathy and isolated complex I deficiency due to de novo hemizygous mutations (c.286C > T and c.328C > T) in the NDUFB11 gene. Neither of them had any skin manifestations. The NDUFB11 gene encodes a relatively small integral membrane protein NDUFB11, which is essential for the assembly of an active complex I. The expression levels of this protein was decreased in both patient cells and a lentiviral complementation experiment also supported the notion that the complex I deficiency in those two patients is caused by NDUFB11 genetic defects. Our findings together with a review of the thirteen previously described patients demonstrate a wide spectrum of clinical features associated with NDUFB11-related complex I deficiency. However, histiocytoid cardiomyopathy and/or congenital sideroblastic anemia could be indicative for mutation in the NDUFB11 gene, while the clinical manifestation of the same mutation can be highly variable. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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