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 form of inherited increase of serum thyroxine in Caucasians. It is the result 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, resulting in the replacement of the normal Arg with His. This mutation was found in 9 affected family members but not in 8 unaffected relatives and 18 unrelated normal individuals. The same missense mutation was found in 12 other subjects with FDH belonging to 7 unrelated families. In every individual with FDH, the mutation was associated with the Sac I+ polymorphism in the albumin gene, strongly suggesting a founder effect.
Sunthornthepvarakul
T
T
Department of Medicine, University of Chicago, IL 60637.
Angkeow
P
P
Weiss
R E
RE
Hayashi
Y
Y
Refetoff
S
S
D001120:Arginine / Q000235:genetics; D003062:Codon; D018076:DNA, Complementary / Q000737:chemistry; D006639:Histidine / Q000235:genetics; D006801:Humans; D006981:Hyperthyroxinemia / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012709:Serum Albumin / Q000235:genetics*; D013974:Thyroxine / Q000097:blood; D014285:Triiodothyronine, Reverse / Q000097:blood
D003062:Codon; D018076:DNA, Complementary; D012709:Serum Albumin; D006639:Histidine; D014285:Triiodothyronine, Reverse; D001120:Arginine; D013974:Thyroxine