Broad phenotypic variability in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1

Kristoffer Björkman; Kalliopi Sofou; Niklas Darin; Elisabeth Holme; Gittan Kollberg; Jorge Asin-Cayuela; Karin M Holmberg Dahle; Anders Oldfors; Ali-Reza Moslemi; Már Tulinius

doi:10.1016/j.mito.2015.01.003

Broad phenotypic variability in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1

Mitochondrion. 2015 Mar:21:33-40. doi: 10.1016/j.mito.2015.01.003. Epub 2015 Jan 20.

Authors

Affiliations

¹ Department of Pediatrics, University of Gothenburg, The Queen Silvia Children's Hospital, Gothenburg, Sweden. Electronic address: kristoffer.bjorkman@gu.se.
² Department of Pediatrics, University of Gothenburg, The Queen Silvia Children's Hospital, Gothenburg, Sweden. Electronic address: kalliopi.sofou@vgregion.se.
³ Department of Pediatrics, University of Gothenburg, The Queen Silvia Children's Hospital, Gothenburg, Sweden. Electronic address: niklas.darin@vgregion.se.
⁴ Department of Clinical Chemistry, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: elisabeth.holme@clinchem.gu.se.
⁵ Department of Clinical Chemistry, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: gittan.kollberg@gu.se.
⁶ Department of Clinical Chemistry, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: jorge.cayuela@clinchem.gu.se.
⁷ Akershus University Hospital, Lørenskog, Norway. Electronic address: karin.m.holmberg.dahle@ahus.no.
⁸ Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: anders.oldfors@gu.se.
⁹ Department of Pathology, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: ali-reza.moslemi@pathology.gu.se.
¹⁰ Department of Pediatrics, University of Gothenburg, The Queen Silvia Children's Hospital, Gothenburg, Sweden. Electronic address: mar.tulinius@vgregion.se.

PMID: 25615419
DOI: 10.1016/j.mito.2015.01.003

Abstract

We report clinical, metabolic, genetic and neuroradiological findings in five patients from three different families with isolated complex I deficiency. Genetic analysis revealed mutations in NDUFS1 in three patients and in NDUFV1 in two patients. Four of the mutations are novel and affect amino acid residues that either are invariant among species or conserved in their properties. The presented clinical courses are characterized by leukoencephalopathy or early death and expand the already heterogeneous phenotypic spectrum. A literature review was performed, showing that patients with mutations in NDUFS1 in general have a worse prognosis than patients with mutations in NDUFV1.

Keywords: Leukoencephalopathies; MITOCHONDRIAL encephalomyopathies; Mitochondrial complex I deficiency; NADH-ubiquinone oxidoreductase Fe–S protein 1 (NDUFS1) mutations; NADH-ubiquinone oxidoreductase flavoprotein 1 (NDUFV1) mutations.

Publication types

Case Reports

MeSH terms

Electron Transport Complex I / deficiency*
Female
Humans
Infant
Infant, Newborn
Leukoencephalopathies / genetics
Leukoencephalopathies / pathology*
Male
Mitochondrial Diseases / genetics
Mitochondrial Diseases / pathology*
Mutant Proteins / genetics
Mutant Proteins / metabolism
NADH Dehydrogenase / genetics*
NADH Dehydrogenase / metabolism*
Survival Analysis

Substances

Mutant Proteins
NDUFS1 protein, human
NDUFV1 protein, human
NADH Dehydrogenase
Electron Transport Complex I