Likely inborn error of metabolism - targeted testing not possible
Gene: NDUFB9Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.
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, 12:39 p.m. | Last Modified: 19 Aug 2019, 12:39 p.m.
Panel Version: 1.195
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 panelCreated: 23 Feb 2017, 5:15 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
?Mitochondrial complex I deficiency
Publications
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: 29 Mar 2019, 11:06 a.m.
Comment on list classification: Pathogenic variant reported in siblings in one publication.Created: 22 Apr 2016, 7:30 a.m.
Comment on list classification: Promoted from red to amber.Created: 22 Apr 2016, 7:17 a.m.
single mutation report in literatureCreated: 4 Feb 2016, 8:37 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Gene: ndufb9 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: NDUFB9 were changed from ?Mitochondrial complex I deficiency, 252010; Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); ?Mitochondrial complex I deficiency; Isolated complex I deficiency to ?Mitochondrial complex I deficiency, nuclear type 24 618245
Publications for gene: NDUFB9 were set to 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.
Source NHS GMS was added to NDUFB9. Source London North GLH was added to NDUFB9.
Sarah Leigh: Associated with relevant pheno
Added phenotypes ?Mitochondrial complex I deficiency, 252010; Isolated complex I deficiency for gene: NDUFB9 Publications for gene NDUFB9 were changed from 27604308 to 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.
gene: NDUFB9 was added gene: NDUFB9 was added to Inborn errors of metabolism. Sources: Expert Review Amber Mode of inheritance for gene: NDUFB9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NDUFB9 were set to 27604308 Phenotypes for gene: NDUFB9 were set to ?Mitochondrial complex I deficiency; Complex I (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits)