title: Homozygous nonsense mutation in the insulin receptor gene in infant with leprechaunism.
abstract: Mutations in the insulin receptor gene have been detected in patients with severe insulin resistance, but the absence of insulin receptors has not been recorded. We report a severely insulin resistant newborn baby, the offspring of consainguineous parents, who was homozygous for a nonsense mutation (Lys 121-Amber) in this gene. Translation of this very truncated N-terminal fragment would not be expected to result in a functional insulin receptor. The infant had all the typical features of the syndrome of leprechaunism. The baby probably represents the null phenotype with respect to the insulin receptor. Because insulin receptors are expressed very early in the developing embryo, the absence of functional insulin receptors is thought to be incompatible with fetal viability: the normal organogenesis in this infant who survived beyond term implies that this assumption is probably incorrect.
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrookes Hospital, UK.
authors.forename: A
authors.initials: A
authors.lastname: Krook
authors.forename: L
authors.initials: L
authors.lastname: Brueton
authors.forename: S
authors.initials: S
authors.lastname: O'Rahilly
mesh_terms: D001483:Base Sequence; D004277:DNA, Single-Stranded; D005145:Face / Q000002:abnormalities; D005317:Fetal Growth Retardation / Q000235:genetics*; D006628:Hirsutism / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011972:Receptor, Insulin / Q000235:genetics*; D013577:Syndrome
chemical_list: D004277:DNA, Single-Stranded; D011972:Receptor, Insulin