Skip Navigation



Human Molecular Genetics Advance Access published online on June 12, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp276
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
18/18/3365    most recent
ddp276v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Janssen, R. J.R.J.
Right arrow Articles by Nijtmans, L. G.J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Janssen, R. J.R.J.
Right arrow Articles by Nijtmans, L. G.J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Contiguous gene deletion of ELOVL7, ERCC8, and NDUFAF2 in a patient with a fatal multisystem disorder

Rolf J.R.J. Janssen1, Felix Distelmaier2,3, Roel Smeets1, Tessa Wijnhoven2, Elsebet Østergaard4, Nicolaas G.J. Jaspers5, Anja Raams5, Stephan Kemp6, Richard J.T. Rodenburg1, Peter H.M.G. Willems2, Lambert P.W.J. van den Heuvel1, Jan A.M. Smeitink1 and Leo G.J. Nijtmans1,*

1 Nijmegen Center for Mitochondrial Disorders at the Department of Pediatrics, Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands 2 Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands 3 Department of General Pediatrics, Heinrich-Heine-University, Düsseldorf, Germany 4 Department of Clinical Genetics, National University Hospital Rigshospitalet, Copenhagen, Denmark 5 Department of Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands 6 Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

* Correspondence to: Leo G.J. Nijtmans, Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Phone: +31-24-3619470/15251; Fax: +31-24-3668532; E-mail: l.nijtmans{at}cukz.umcn.nl

Received April 8, 2009; Revised June 6, 2009; Accepted June 8, 2009

Contiguous gene syndromes affecting the mitochondrial oxidative phosphorylation system have been rarely reported. Here, we describe a patient with apparent mitochondrial encephalomyopathy accompanied by several unusual features, including dysmorphism and hepatopathy, caused by a homozygous triple gene deletion on chromosome 5. The deletion encompassed the NDUFAF2, ERCC8, and ELOVL7 genes, encoding complex I assembly factor 2 (also known as human B17.2L), a protein of the transcription-coupled nucleotide excision repair (TC-NER) machinery, and a putative elongase of very long-chain fatty acid synthesis, respectively. Detailed evaluation of cultured skin fibroblasts revealed disturbed complex I assembly, depolarization of the mitochondrial membrane, elevated cellular NAD(P)H level, increased superoxide production, and defective TC-NER. ELOVL7 mRNA was not detectable in these cells and no alterations in fatty acid synthesis were found. By means of baculoviral complementation we were able to restore the aberrations, thereby establishing causative links between genotype and cell-physiological phenotype. This first chromosomal microdeletion illustrates that beside primary defects in mitochondrial genes also additional genes possibly contribute to the disease phenotype, providing an additional explanation for the broad clinical symptoms associated with these disorders.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.