Inherited white matter disorders

Gene: NDUFV1

Comment on list classification: Gene rated green and diagnostic-grade by expert reviewer, confirmed DD gene for MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY. On the Minimum recommended gene list for broad spectrum genetic testing for single-nucleotide variants associated with leukodystrophies and genetic leukoencephalopathies reported in PMID: 25655951 for Mitochondrial complex I disorders. Green gene in the Mitochondrial panel version 1.10. 2 compound heterozygous reports on OMIM for 4 different variants, however OMIM has an additional report of a pathogenic variant that has been reclassified due to a yeast model study (PMID: 26345448). Results from the yeast model system challenged the assignment of 5 of the 19 variants investigated (S56P, K111E, R147W, R199P and A341V) as pathogenic, suggesting the need for further investigation in these cases (PMID: 26345448). The paper also discusses the limitations of the system and comparison with the clinical cases. The 6 variants for 4 patients classifed on OMIM and reported in PMID: 27344648 do not include the 5 variants highlighted in PMID: 26345448 as potentially not pathogenic. Therefore the role of the gene is not being challenged, rather the consequence of some missense variants within this gene that have been reported as pathogenic.

Created: 19 Aug 2016, 11:19 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
General Leukodystrophy & Mitochondrial Leukoencephalopathy

Publications

• Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_656

Variants in this GENE are reported as part of current diagnostic practice