title: Alternative splicing of the insulin receptor isoforms is altered in patients with leprechaunism.
abstract: Leprechaunism is a syndrome of severe insulin resistance. In general, mutations in both alleles of the insulin receptor are required for developing the leprechaun phenotype. Recently, we described a leprechaun patient having an Arg for Gly substitution in one allele of the insulin receptor whereas the other allele has the normal sequence. To explain the leprechaun phenotype, we searched for additional defects at the receptor level. The insulin receptor exists as two splice variants, either with (B form) or without exon 11 (A form). It has been suggested that a decrease in the relative amount of the A isoform can contribute to the development of an insulin resistant state. Fibroblasts from the leprechaun patient show levels of the A isoform of less than 20% whereas in control fibroblasts approximately 50% of the A isoform is present. However, in fibroblasts from two other patients with severe insulin resistance where the disease has been demonstrated to result from two mutated insulin receptor alleles, the same decline of the A isoform was seen. We conclude that the decrease in the relative amount of the A isoform in these patients is probably an epiphenomenon due to impaired insulin action.
authors.affiliation: Department of Medical Biochemistry, Sylvius Laboratories, Leiden, The Netherlands.
authors.forename: E R
authors.initials: ER
authors.lastname: van der Vorm
authors.forename: J A
authors.initials: JA
authors.lastname: Maassen
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification; D005091:Exons / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D007536:Isomerism; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism
chemical_list: D012313:RNA; D004247:DNA; D011972:Receptor, Insulin