title: New insights into the genetics of 5-oxoprolinase deficiency and further evidence that it is a benign biochemical condition.
abstract: Inherited 5-oxoprolinase (OPLAH) deficiency is a rare inborn condition characterised by 5-oxoprolinuria. To date, three OPLAH mutations have been described: p.H870Pfs in a homozygous state, which results in a truncated protein, was reported in two siblings, and two heterozygous missense changes, p.S323R and p.V1089I, were independently identified in two unrelated patients. We describe the clinical context of a young girl who manifested 5-oxoprolinuria together with dusky episodes and who is compound heterozygote for two novel OPLAH variations: p.G860R and p.D1241V. To gain insight into the aetiology of the 5-oxoprolinase deficiency, we investigated the pathogenicity of all the reported missense mutations in the OPLAH gene. A yeast in vivo growth assay revealed that only p.S323R, p.G860R and p.D1241V affected the activity of the enzyme.
  
  
  CONCLUSIONS
  Taken together, this report further suggests that hereditary 5-oxoprolinase deficiency is a benign biochemical condition caused by mutations in the OPLAH gene, which are transmitted in an autosomal recessive manner, but 5-oxoprolinuria may be a chance association in other disorders.
authors.affiliation: Program in Rare and Genetic Diseases, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain, ecalpena@cipf.es.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Calpena
authors.forename: Anup Arunrao
authors.initials: AA
authors.lastname: Deshpande
authors.forename: Sufin
authors.initials: S
authors.lastname: Yap
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Kumar
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Manning
authors.forename: Anand K
authors.initials: AK
authors.lastname: Bachhawat
authors.forename: Carmen
authors.initials: C
authors.lastname: Espinós
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007223:Infant; D020125:Mutation, Missense; D011752:Pyroglutamate Hydrolase / Q000172:deficiency* / Q000235:genetics
chemical_list: D011752:Pyroglutamate Hydrolase