Identification of two novel insulin receptor mutations, Asp59Gly and Leu62Pro, in type A syndrome of extreme insulin resistance.
Biochem Biophys Res Commun
; 234(3): 764-8, 1997 May 29.
Article
em En
| MEDLINE
| ID: mdl-9175790
ABSTRACT
To elucidate genetic determinants of insulin resistance, we investigated insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) genes, in vitro IR function and in vivo insulin sensitivity in a family with Type A syndrome. Two missense IR mutations (Asp59Gly and Leu62Pro) found in the proband, resulted in reduction by 90% of insulin binding to erythrocytes, decreased receptor autophosphorylation and a dramatic reduction of insulin sensitivity. The proband and mother were heterozygote for Gly972Arg IRS-1 variant. Asp59Gly mutation, also carried by proband's brother with no consequence on insulin sensitivity, was inherited from the mother who is diabetic and insulin resistant and Leu62Pro was from the father. We conclude that severity of insulin resistance in the proband may be explained by the genetic condition of compound heterozygote for IR mutations while severe insulin resistance in the mother raises the possibility that other genetic factors, like IRS-1 polymorphisms, may contribute to the phenotypic expression of IR mutations.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Receptor de Insulina
/
Mutação Puntual
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Child
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
França