Undiagnosed metabolic disordersGene: OPLAH
Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants have been reported. It is not clear whether the mode of inheritance is biallelic or monoallelic as homozygous and heterozygote cases have been seen. The PMID 21651516 reports two sibs who are homozygous for a terminating variant, the younger brother is 5-oxoprolinase deficiency, however, his clinically unaffected sister just has increased 5-oxoproline excretion.
Created: 19 Aug 2019, 1:41 p.m. | Last Modified: 19 Aug 2019, 1:41 p.m.
Panel Version: 1.216
Comment on phenotypes: Oxoprolinuria (Disorders of the gamma-glutamyl cycle)
Created: 19 Aug 2019, 1:40 p.m. | Last Modified: 19 Aug 2019, 1:40 p.m.
Panel Version: 1.214
21651516 (1 affected); 23430506 (2 unrelated affecteds), 3 different variants reported- phenotype results in low activity of 5-oxoprolinase. Variants also reported in unaffected subjects, maybe due to phenotypic variablilty. On Radboud MENDELIOME/MCA METABOLIC DISORDERS panel. Omim contacted for clarification of MOI and of gene / phenotype association
Created: 23 Feb 2017, 5:15 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
5-oxoprolinase deficiency, 260005
Gene: oplah has been classified as Amber List (Moderate Evidence).
Publications for gene: OPLAH were set to 27604308
Phenotypes for gene: OPLAH were changed from Oxoprolinuria (Disorders of the gamma-glutamyl cycle); 5-oxoprolinase deficiency, 260005 to 5-oxoprolinase deficiency 260005
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
OPLAH was added to Undiagnosed metabolic disorderspanel. Source: Expert Review Amber OPLAH was added to Undiagnosed metabolic disorderspanel. Source: Radboud University Medical Center, Nijmegen Model of inheritance for gene OPLAH was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
OPLAH was added to Undiagnosed metabolic disorderspanel. Sources: Literature
OPLAH was created by sleigh