Ardon et al. (2014) stated that this mutation is c.338G-C in exon 2 and results in an amino acid change arg113 to pro (R113P), according to a revised INSR sequence (GenBank NC_000019).
Fibroblasts cultured from a patient with Donohue syndrome (246200) with intrauterine growth retardation and severe insulin resistance (designated leprechaun Atlanta (Atl)-1) had normal amounts of insulin receptor protein and defective insulin binding but constitutive activation of insulin-receptor autophosphorylation and kinase activity and of glucose transport (Longo et al., 1993). In the same fibroblasts, growth was impaired. Homozygosity for a mutation in the INSR gene was suspected, since he inherited identical DNA haplotypes for this gene from the parents who were blood relatives. Longo et al. (1993) found that indeed the proband was homozygous and both parents were heterozygous for a G-to-C transversion at nucleotide 476 of the INSR cDNA converting arginine-86 to proline (ARG86PRO, R86P). Expression of this mutation in CHO cells duplicated the natural mutation by activating glucose transport without increasing insulin binding or insulin-stimulated cellular growth. The R86P substitution is contiguous to the hydrophobic beta-sheet of the receptor alpha subunit implicated in the binding of aromatic residues of the insulin molecule.
