title: TBG deficiency: description of two novel mutations associated with complete TBG deficiency and review of the literature.
abstract: Thyroxine-binding globulin (TBG) is the main thyroid hormone transport protein in serum. Inherited TBG defects lead to a complete (TBG-CD) or a partial (TBG-PD) deficiency and have a diagenic transmission, being clinically fully expressed only in hemizygous males and in homozygous females. In the present study, seven patients from two unrelated families with TBG-CD were studied and two novel TBG mutations were documented. In particular, a T insertion at the 5' donor splice site of exon 0, between nucleotides 2 and 3 at the beginning of intron 1 (g.IVS1+2_3insT) was found in one family and was named TBG-Milano. The other novel mutation is a T deletion at nucleotide 214 of exon 1, which leads to a frameshift at codon 50 with a premature stop codon at position 51 (c.214delT, P50fsX51) and was named TBG-Nikita. According to the X-linked transmission of the defect, females harboring the mutation showed a reduction in TBG levels with normal TSH and total thyroid hormone values at the lower limit of normal. Males harboring either TBG-Milano or TBG-Nikita, showed normal TSH values and low levels of total thyroid hormones and lacked TBG. In conclusion, we report two novel mutations of the TBG gene associated with a complete TBG defect. The first mutation lies at the 5' donor splice site of exon 0 and probably alters the start of translation, while the second is a single nucleotide deletion and leads to a premature stop codon.
authors.affiliation: Institute of Endocrine Sciences, University of Milan, Pad. Granelli Via F. Sforza, 35, Milan, 20122, Italy.
authors.forename: Deborah
authors.initials: D
authors.lastname: Mannavola
authors.forename: Guia
authors.initials: G
authors.lastname: Vannucchi
authors.forename: Laura
authors.initials: L
authors.lastname: Fugazzola
authors.forename: Valentina
authors.initials: V
authors.lastname: Cirello
authors.forename: Irene
authors.initials: I
authors.lastname: Campi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Radetti
authors.forename: Luca
authors.initials: L
authors.lastname: Persani
authors.forename: Samuel
authors.initials: S
authors.lastname: Refetoff
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
mesh_terms: D000368:Aged; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010375:Pedigree; D013975:Thyroxine-Binding Proteins / Q000172:deficiency* / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D013975:Thyroxine-Binding Proteins