Type I hyperprolinemia: genotype/phenotype correlations.
Hum Mutat
; 31(8): 961-5, 2010 Aug.
Article
en En
| MEDLINE
| ID: mdl-20524212
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Prolina
/
Estudios de Asociación Genética
/
Errores Innatos del Metabolismo de los Aminoácidos
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Adult
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Child
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Child, preschool
/
Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Hum Mutat
Asunto de la revista:
GENETICA MEDICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Francia