A novel variant in Serpina7 gene in a family with thyroxine-binding globulin deficiency.
Thyroxine-binding globulin (TBG) carries approximately 75% of serum T4 and T3. This protein is encoded by serpina7 gene, formerly known as TBG gene, localized on X-chromosome (Xq22.2). A deficiency in TBG is suspected when abnormally low serum total T4 and T3 are encountered in clinically euthyroid subjects in the presence of normal serum TSH. This condition has been associated with different serpina7 gene mutations resulting in amino acid substitutions or truncations in the mature protein. Herein, we report a new serpina7 gene variant in three members of the same family. It results in the replacement of the normal asparagine 233 by isoleucine and, subsequently, in disruption of a glycosylation site. Co-segregation of this new variant with undetectable levels of TBG in the hemizygous man studied and failure to recognize the same variant in 100 alleles at random, made us to consider it as the underlying cause of the TBG deficiency.
Domingues
Rita
R
Portuguese Institute of Oncology of Lisbon Francisco Gentil, Lisbon, Portugal. rdomingues@ipolisboa.min-saude.pt
Font
Paula
P
Sobrinho
Luís
L
Bugalho
Maria João
MJ
D000293:Adolescent; D005192:Family Health; D005260:Female; D014644:Genetic Variation; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D013960:Thyroid Function Tests; D013974:Thyroxine / Q000097:blood; D056825:Thyroxine-Binding Globulin; D013975:Thyroxine-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D014284:Triiodothyronine / Q000097:blood; D055815:Young Adult
C534944:SERPINA7 protein, human; D056825:Thyroxine-Binding Globulin; D013975:Thyroxine-Binding Proteins; D014284:Triiodothyronine; D013974:Thyroxine