New insights into the genetics of 5-oxoprolinase deficiency and further evidence that it is a benign biochemical condition.
Eur J Pediatr
; 174(3): 407-11, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25129617
ABSTRACT
UNLABELLED 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. CONCLUSION:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piroglutamato Hidrolase
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Mutação de Sentido Incorreto
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Erros Inatos do Metabolismo dos Aminoácidos
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Infant
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article