Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency--a neurometabolic disorder associated with reduced L-serine biosynthesis.
Am J Hum Genet
; 67(6): 1389-99, 2000 Dec.
Article
em En
| MEDLINE
| ID: mdl-11055895
ABSTRACT
3-phosphoglycerate dehydrogenase (PHGDH) deficiency is a disorder of L-serine biosynthesis that is characterized by congenital microcephaly, psychomotor retardation, and seizures. To investigate the molecular basis for this disorder, the PHGDH mRNA sequence was characterized, and six patients from four families were analyzed for sequence variations. Five patients from three different families were homozygous for a single nucleotide substitution predicted to change valine at position 490 to methionine. The sixth patient was homozygous for a valine to methionine substitution at position 425; both mutations are located in the carboxyterminal part of PHGDH. In vitro expression of these mutant proteins resulted in significant reduction of PHGDH enzyme activities. RNA-blot analysis indicated abundant expression of PHGDH in adult and fetal brain tissue. Taken together with the severe neurological impairment in our patients, the data presented in this paper suggest an important role for PHGDH activity and L-serine biosynthesis in the metabolism, development, and function of the central nervous system.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Serina
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Desidrogenases de Carboidrato
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Erros Inatos do Metabolismo dos Aminoácidos
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Mutação
Tipo de estudo:
Risk_factors_studies
Limite:
Child, preschool
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Female
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Humans
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Male
País como assunto:
Africa
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Asia
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article