title: A novel missense mutation in codon 218 of the albumin gene in a distinct phenotype of familial dysalbuminemic hyperthyroxinemia in a Japanese kindred.
abstract: Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasians. To our knowledge, no such documentation on Asians exists. Six of 8 members of a 3-generation Japanese family were found by us to carry the FDH phenotype. Serum total T4 levels ranged from 1763.2-2741.3 nmol/L (normal range, 65.6-164.7), serum total T3 levels ranged from 2.73-5.62 nmol/L (normal range, 1.47-2.95), and rT3 levels ranged from 1.08-2.52 nmol/L (normal range, 0.22-0.60). In the proband, the majority of [125I]T4 in serum T4-binding proteins was distributed in albumin fractions, and the isolated albumin had an increased affinity for T4. A guanine to cytosine transition in the second nucleotide of codon 218, resulting in replacement of normal arginine with proline, was detected in 1 of 2 alleles in all 5 subjects of the family with FDH. In all FDH-affected Caucasian subjects from 10 unrelated families with a moderate increase in serum T4, the guanine to adenine transition was demonstrated at the same position of the albumin gene as noted in our patients, but histidine, the replacement amino acid, differed from proline noted in our FDH Japanese subjects. It would thus appear that FDH has ethnic variations.
authors.affiliation: Department of Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Wada
authors.forename: H
authors.initials: H
authors.lastname: Chiba
authors.forename: C
authors.initials: C
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Kijima
authors.forename: M
authors.initials: M
authors.lastname: Kubo
authors.forename: T
authors.initials: T
authors.lastname: Koike
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People; D002352:Carrier Proteins / Q000097:blood; D003062:Codon; D005260:Female; D016678:Genome; D006801:Humans; D006981:Hyperthyroxinemia / Q000208:ethnology / Q000209:etiology* / Q000235:genetics*; D007564:Japan / Q000208:ethnology; D008565:Membrane Proteins / Q000097:blood; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012709:Serum Albumin / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000503:physiopathology; D013963:Thyroid Hormones; D013974:Thyroxine / Q000097:blood / Q000378:metabolism; D014284:Triiodothyronine / Q000097:blood; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D003062:Codon; D008565:Membrane Proteins; D012709:Serum Albumin; D013963:Thyroid Hormones; D013974:Thyroxine; D014284:Triiodothyronine; D000097810:Thyroid Hormone-Binding Proteins