Type I hyperprolinemia: genotype/phenotype correlations.

Détails

ID Serval
serval:BIB_1375E5CC31AE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Type I hyperprolinemia: genotype/phenotype correlations.
Périodique
Human Mutation
Auteur(s)
Guilmatre A., Legallic S., Steel G., Willis A., Di Rosa G., Goldenberg A., Drouin-Garraud V., Guet A., Mignot C., Des Portes V., Valayannopoulos V., Van Maldergem L., Hoffman J.D., Izzi C., Espil-Taris C., Orcesi S., Bonafé L., Le Galloudec E., Maurey H., Ioos C., Afenjar A., Blanchet P., Echenne B., Roubertie A., Frebourg T., Valle D., Campion D.
ISSN
1098-1004[electronic], 1059-7794[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
31
Numéro
8
Pages
961-965
Langue
anglais
Notes
Publication types: Journal Article
Résumé
Type I hyperprolinemia (HPI) is an autosomal recessive disorder associated with cognitive and psychiatric troubles, caused by alterations of the Proline Dehydrogenase gene (PRODH) at 22q11. HPI results from PRODH deletion and/or missense mutations reducing proline oxidase (POX) activity. The goals of this study were first to measure in controls the frequency of PRODH variations described in HPI patients, second to assess the functional effect of PRODH mutations on POX activity, and finally to establish genotype/enzymatic activity correlations in a new series of HPI patients. Eight of 14 variants occurred at polymorphic frequency in 114 controls. POX activity was determined for six novel mutations and two haplotypes. The c.1331G>A, p.G444D allele has a drastic effect, whereas the c.23C>T, p.P8L allele and the c.[56C>A; 172G>A], p.[Q19P; A58T] haplotype result in a moderate decrease in activity. Among the 19 HPI patients, 10 had a predicted residual activity <50%. Eight out of nine subjects with a predicted residual activity > or = 50% bore at least one c.824C>A, p.T275N allele, which has no detrimental effect on activity but whose frequency in controls is only 3%. Our results suggest that PRODH mutations lead to a decreased POX activity or affect other biological parameters causing hyperprolinemia.
Mots-clé
Adolescent, Adult, Alleles, Amino Acid Metabolism, Inborn Errors/enzymology, Amino Acid Metabolism, Inborn Errors/genetics, Case-Control Studies, Child, Child, Preschool, Female, Genetic Association Studies, Humans, Infant, Male, Mutation, Missense/genetics, Proline/metabolism, Proline Oxidase/genetics
Pubmed
Web of science
Création de la notice
16/02/2011 11:06
Dernière modification de la notice
20/08/2019 13:42
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