Dataset Information

NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern.

ABSTRACT: To identify the mutated gene in a group of patients with an unclassified heritable white matter disorder sharing the same, distinct MRI pattern.We used MRI pattern recognition analysis to select a group of patients with a similar, characteristic MRI pattern. We performed whole-exome sequencing to identify the mutated gene. We examined patients' fibroblasts for biochemical consequences of the mutant protein.We identified 6 patients from 5 unrelated families with a similar MRI pattern showing predominant abnormalities of the cerebellar cortex, deep cerebral white matter, and corpus callosum. The 4 tested patients had a respiratory chain complex ? deficiency. Exome sequencing revealed mutations in NUBPL, encoding an iron-sulfur cluster assembly factor for complex ?, in all patients. Upon identification of the mutated gene, we analyzed the MRI of a previously published case with NUBPL mutations and found exactly the same pattern. A strongly decreased amount of NUBPL protein and fully assembled complex I was found in patients' fibroblasts. Analysis of the effect of mutated NUBPL on the assembly of the peripheral arm of complex I indicated that NUBPL is involved in assembly of iron-sulfur clusters early in the complex I assembly pathway.Our data show that NUBPL mutations are associated with a unique, consistent, and recognizable MRI pattern, which facilitates fast diagnosis and obviates the need for other tests, including assessment of mitochondrial complex activities in muscle or fibroblasts.

SUBMITTER: Kevelam SH

PROVIDER: S-EPMC3662327 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern.

Kevelam Sietske H SH Rodenburg Richard J RJ Wolf Nicole I NI Ferreira Patrick P Lunsing Roelineke J RJ Nijtmans Leo G LG Mitchell Anne A Arroyo Hugo A HA Rating Dietz D Vanderver Adeline A van Berkel Carola G M CG Abbink Truus E M TE Heutink Peter P van der Knaap Marjo S MS

Neurology 20130403 17

<h4>Objective</h4>To identify the mutated gene in a group of patients with an unclassified heritable white matter disorder sharing the same, distinct MRI pattern.<h4>Methods</h4>We used MRI pattern recognition analysis to select a group of patients with a similar, characteristic MRI pattern. We performed whole-exome sequencing to identify the mutated gene. We examined patients' fibroblasts for biochemical consequences of the mutant protein.<h4>Results</h4>We identified 6 patients from 5 unrelate ...[more]

PMID: 23553477

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NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern.

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NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern.

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