caa a22 4500 465804977 CHVBK 20180323112101.0 cr unu---uuuuu 170327e19900401xx s 000 0 eng 10.1007/BF03349576 doi (NATIONALLICENCE)springer-10.1007/BF03349576 Molecular basis for the properties of the thyroxine-binding globulin-slow variant in American Blacks [Elektronische Daten] [M. Waltz, T. Pullman, K. Takeda, P. Sobieszczyk, S. Refetoff] Thyroxine — binding globulin — slow (TBG-S), a variant found in 4-12% of Black and Pacific Island populations, is inherited as an X-chromosome linked trait. This variant is detected on isoelectric focusing by the characteristic cathodal shift of all its isoforms, suggesting that the difference resides in the core protein. In addition, TBG-S is slightly more thermolabile, which explains why subjects expressing TBG-S have on the average lower serum TBG, and thus reduced T4, concentrations. We now report the molecular basis for this TBG variant, deduced from sequencing the TBG-S gene of an American Black man. Sequencing of the four coding regions and all intron/exon junctions revealed a single nucleotide substitution in the codon for amino acid 171 of the mature protein. The resulting change of the codon GAC to AAC results in replacement of the normal aspartic acid by asparagine. Since the negative charge provided by the aspartic acid is lost when replaced.by the neutral asparagine, this substitution seems responsible for the cathodal shift on isoelectric focusing and slower electrophoretic mobility of TBG-S. An identical nucleotide substitution was identified in an unrelated American Black man expressing TBG-S. Whether the TBG-S phenotype observed in populations from the Pacific Islands is caused by the same mutation remains to be determined. Italian Society of Endocrinology (SIE), 1990 Thyroxine binding globulin nationallicence variant nationallicence African American nationallicence Isoelectric focusing nationallicence sequencing nationallicence mutation nationallicence Waltz M. Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Box 138, 60637, Chicago, IL, USA aut Pullman T. Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Box 138, 60637, Chicago, IL, USA aut Takeda K. Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Box 138, 60637, Chicago, IL, USA aut Sobieszczyk P. Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Box 138, 60637, Chicago, IL, USA aut Refetoff S. Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Box 138, 60637, Chicago, IL, USA aut Journal of Endocrinological Investigation Springer International Publishing 13/4(1990-04-01), 343-349 0391-4097 13:4<343 1990 13 40618 https://doi.org/10.1007/BF03349576 text/html Onlinezugriff via DOI 1 brief-communication jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF03349576 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Waltz M. Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Box 138, 60637, Chicago, IL, USA aut NATIONALLICENCE 700 1- Pullman T. Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Box 138, 60637, Chicago, IL, USA aut NATIONALLICENCE 700 1- Takeda K. Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Box 138, 60637, Chicago, IL, USA aut NATIONALLICENCE 700 1- Sobieszczyk P. Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Box 138, 60637, Chicago, IL, USA aut NATIONALLICENCE 700 1- Refetoff S. Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Box 138, 60637, Chicago, IL, USA aut NATIONALLICENCE 773 0- Journal of Endocrinological Investigation Springer International Publishing 13/4(1990-04-01), 343-349 0391-4097 13:4<343 1990 13 40618 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer