Summary
The variant thyroxine-binding globulin in a family from Montreal (TBG-M) has a reduced affinity for thyroxine, shows a slight cathodal shift on isoelectric focusing, and has an increased susceptibility to inactivation by heat and acid. We present the molecular basis for TBG-M, deduced by sequencing the entire 1245-bp coding regions and intron/exon junctions of the TBG gene of an affected hemizygous male. A single nucleotide substitution in the codon for amino acid 113 of the mature protein (GCC to CCC) was found, resulting in the replacement of alanine by proline. The mutation was confirmed by allele-specific amplification of genomic DNA from the propositus and three other affected family members. Since point mutations throughout the molecule have been shown to alter the properties of variant TBGS, and because amino acid substitutions with proline are known to impair stability and function of proteins, the replacement of alanine 113 by proline provides a logical explanation for the observed properties of TBG-M.
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Janssen, O.E., Takeda, K. & Refetoff, S. Sequence of the variant thyroxine-binding globulin (TBG) in a Montreal family with partial TBG deficiency. Hum Genet 87, 119–122 (1991). https://doi.org/10.1007/BF00204164
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DOI: https://doi.org/10.1007/BF00204164