AN IDENTICAL MISSENSE MUTATION IN THE ALBUMIN GENE RESULTS IN FAMILIAL DYSALBUMINEMIC HYPERTHYROXINEMIA IN 8 UNRELATED FAMILIES

Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common far m of inherited increase of serum thyroxine in Caucasians, It is the re sult of increased thyroxine-binding to serum proteins and is inherited as a dominant trait. The entire coding region of the albumin gene of a subject with FDH was sequenced. A single nucleotide substitution, G to A transition in codon 218, was found in one of the two alleles, res ulting in the replacement of the normal Arg with His. This mutation wa s found in 9 affected family members but not in 8 unaffected relatives and 18 unrelated normal individuals. The same missense mutation was f ound in 12 other subjects with FDH belonging to 7 unrelated families. In every individual with FDH, the mutation was associated with the Sac (C) 1994 Academic Press, Inc.