DECREASED CORTISOL-BINDING AFFINITY OF TRANSCORTIN LEUVEN IS ASSOCIATED WITH AN AMINO-ACID SUBSTITUTION AT RESIDUE-93

Genomic DNA was isolated from two related individuals who are homozygo us for transcortin Leuven, a corticosteroid-binding globulin variant w ith decreased cortisol-binding affinity. This material was amplified u sing intron-specific oligonucleotide primers in a polymerase chain rea ction to obtain the four exons that encode transcortin. Sequence analy sis of these exons showed several mutations within the coding sequence of both individuals, but only one of these will result in an amino ac id substitution. This mutation is located within exon 2 and alters the codon (CTC) normally associated with Leu-93 in the transcortin polype ptide to a codon (CAC) for histidine in the variant genes.