Undiagnosed metabolic disordersGene: NDUFB9
Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 variant reported, together with supportive functional studies.
Created: 19 Aug 2019, 12:40 p.m. | Last Modified: 19 Aug 2019, 12:40 p.m.
Panel Version: 1.210
Comment on publications: PMID: 22200994 Reports one probound heterozygous for a variant (c.140G>T, p.Arg47Leu) within NDUFB9 with parents not available for genetic testing, and in vitro complement studies in patient fibroblasts showed wildtype NDUFB9 did not rescue complex I activity, therefore was deemed not pathogenic. Reports two brothers homozygous for a variant in the gene, with parents who are heterozygous carriers (c.191T>C, p.Leu64Pro). In vitro, fibroblasts from the proband showed low complex I activity, and wildtype NDUFB9 rescued complex I activity.
Created: 19 Aug 2019, 12:39 p.m. | Last Modified: 19 Aug 2019, 12:39 p.m.
Panel Version: 1.209
currently phenotype and gene is provisional in OMIM (last update 2013), to date there is only one reported case : PMID:22200994 1 family (2 affected) homozygous c.191T>C, p.(L64P) (highly conserved residue). Phenotype rescued by wild type NDUFB9 in patient derived fibroblasts. On Radboud EPILEPSY MITOCHONDRIAL DISORDERS panel
Created: 23 Feb 2017, 5:15 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
?Mitochondrial complex I deficiency
Gene: ndufb9 has been classified as Amber List (Moderate Evidence).
Publications for gene: NDUFB9 were set to 27604308
Phenotypes for gene: NDUFB9 were changed from Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); ?Mitochondrial complex I deficiency to ?Mitochondrial complex I deficiency, nuclear type 24 618245
Construction of “Undiagnosed Metabolic Disorders” (UDM) panel • The 614 genes from the neurometabolic gene panel (PMID: 27604308) added • Green genes downloaded from V1 metabolic panels (Cerebral folate deficiency, Congenital disorders of glycosylation, Hyperammonaemia, Ketotic hypoglycaemia, Mitochondrial disorders, Mucopolysaccharideosis, Gaucher, Fabry, Peroxisomal disorders), sources replaced with "Expert review green", then loaded as a review onto UDM panel, resulting in 367 green genes and 333 red (therefore 86 new green genes included from the additional metabolic panels that weren't previously on the UDM panel) • Downloaded green genes from all panels. Removed genes from none V1 panels. Removed genes from the metabolic panels mentioned above. Compared the remaining genes with the red genes from UDM panel. Loaded as an "Expert review Amber" review to the overlapping genes, (the panel name where the genes came from was used as the phenotype) • Used variant information from PMID 27604308 to review the genes on this panel • Reviewed genes on UDM panel with genes from Emory "Inherited Metabolic Disorders: Sequencing Panel" and UKGTN “Inborn Errors of Metabolism 226 panel”, changing status where appropriate, added 14 UKGTN genes that had not be listed before • Review 10 red genes that had not previously been reviewed, 4/10 were reclassified as green • Review the remaining 145 red genes that had not previously been reviewed (shared between reviewers EM, RF, LD, AT, HB, ON & SL), resulting in 60 green, 11 amber, 70 red, 4 I don’t know reviews) • Reviewed genes from PMID: 24816252 as a publication to genes found in the Inborn error or metabolism Genes metabolomics GWAS paper (figure 5). 2 new genes added
NDUFB9 was added to Undiagnosed metabolic disorderspanel. Source: Expert Review Amber NDUFB9 was added to Undiagnosed metabolic disorderspanel. Source: Radboud University Medical Center, Nijmegen Model of inheritance for gene NDUFB9 was set to BIALLELIC, autosomal or pseudoautosomal
NDUFB9 was created by sleigh
NDUFB9 was added to Undiagnosed metabolic disorderspanel. Sources: Literature