NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern
Sietske H Kevelam1, Richard J Rodenburg, Nicole I Wolf
1Department of Child Neurology, VU University Medical Center, Amsterdam, the Netherlands.
Neurology
|April 5, 2013
Summary
Mutations in the NUBPL gene cause a distinct white matter disorder identifiable by MRI. This finding aids in rapid diagnosis of this rare neurological condition.
Area of Science:
- Neurogenetics
- Neuroimaging
- Mitochondrial Biology
Background:
- Unclassified heritable white matter disorders present diagnostic challenges.
- Distinct neuroimaging patterns can indicate specific genetic causes.
- Mitochondrial respiratory chain complex deficiencies are linked to neurological dysfunction.
Purpose of the Study:
- To identify the genetic cause of a rare white matter disorder with a characteristic MRI pattern.
- To investigate the role of NUBPL in mitochondrial complex I assembly.
Main Methods:
- MRI pattern recognition to select patient cohorts.
- Whole-exome sequencing for mutation identification.
- Fibroblast analysis to assess biochemical consequences of mutations.
Main Results:
- Identified NUBPL mutations in 6 patients from 5 families with a consistent MRI pattern.
- Patients exhibited respiratory chain complex I deficiency.
- NUBPL mutations impair iron-sulfur cluster assembly in complex I.
Conclusions:
- NUBPL mutations are associated with a unique and recognizable MRI pattern.
- This MRI pattern facilitates rapid diagnosis of NUBPL-related disorders.
- Diagnosis can be made without invasive biochemical testing.
Related Concept Videos
01:15Insensitive Nuclei Enhanced by Polarization Transfer (INEPT)
Insensitive Nuclei Enhanced by Polarization Transfer (INEPT) is an advanced Nuclear Magnetic Resonance (NMR) technique specifically designed to detect and enhance the signals of low-abundance nuclei, such as carbon-13 and nitrogen-15, in small molecules. The fundamental principle behind INEPT is the transfer of polarization from a more abundant and highly polarizable nucleus, typically hydrogen-1, to the low-abundance nucleus of interest. This process effectively boosts the NMR signal of the...
01:24Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is a noninvasive medical imaging technique based on a phenomenon of nuclear physics discovered in the 1930s, in which matter exposed to magnetic fields and radio waves was found to emit radio signals. In 1970, a physician and researcher named Raymond Damadian noticed that malignant (cancerous) tissue gave off different signals than normal body tissue. He applied for a patent for the first MRI scanning device in clinical use by the early 1980s. The early MRI...