title: Novel mutation p.A64D in the Serpina7 gene as a cause of partial thyroxine-binding globulin deficiency associated with increases affinity in transthyretin by a known p.A109T mutation in the TTR gene.
abstract: Partial thyroxine-binding globulin deficiency (TBG-PD) is an endocrine defect with a prevalence of 1:4 000 in newborns. Due to the presence of a single TBG gene on the X chromosome, most familial TBG defects follow an X-linked inheritance pattern. Abnormal T4 binding to T4-binding prealbumin (TTR) is a rare cause of euthyroid hyperthyroxinemia, which is transmitted by autosomal dominant inheritance. The purpose of the present study was to identify and characterize new mutations in the Serpina7 and TTR genes in a complete family with typical TBG-PD. All patients underwent clinical and biochemical evaluation. Sequencing of DNA, population screening by (SSCP) analysis, and bioinformatics studies were performed. Molecular studies revealed a novel p.A64D mutation in the exon 1 of Serpina7 gene associated with the previously reported p.A109T mutation in the exon 4 of TTR gene. To our knowledge, this is the first report of a patient with a TBG-PD by a mutation in Serpina7 that was coincident with a mutation in TTR gene that increased affinity of TTR for T4. This work contributes to elucidate the molecular basis of the defects of thyroid hormone transport in serum and the improvement of the diagnosis avoiding unnecessary therapy.
authors.affiliation: Servicio de Endocrinología, Departamento de Medicina, Hospital General de Agudos "Dr. Enrique Tornú", C1427ARN Buenos Aires, Argentina.
authors.forename: R T
authors.initials: RT
authors.lastname: Sklate
authors.affiliation: Laboratorio de Genética y Biología Molecular, Instituto de Inmunología, Genética y Metabolismo (INIGEM, CONICET-UBA), Hospital de Clínicas "José de San -Martín", C1120AAR Buenos Aires, Argentina.
authors.forename: M C
authors.initials: MC
authors.lastname: Olcese
authors.affiliation: División Laboratorio, Hospital General de Agudos "Dr. Carlos G. Durand", C1405DCS Buenos Aires, Argentina.
authors.forename: G C
authors.initials: GC
authors.lastname: Maccallini
authors.affiliation: Unidad de Medicina Molecular-Departamento de Medicina, IBMCC and IBSAL. Universidad de Salamanca-CSIC, Salamanca, España.
authors.forename: R G
authors.initials: RG
authors.lastname: Sarmiento
authors.affiliation: Laboratorio de Genética y Biología Molecular, Instituto de Inmunología, Genética y Metabolismo (INIGEM, CONICET-UBA), Hospital de Clínicas "José de San -Martín", C1120AAR Buenos Aires, Argentina.
authors.forename: H M
authors.initials: HM
authors.lastname: Targovnik
authors.affiliation: Laboratorio de Genética y Biología Molecular, Instituto de Inmunología, Genética y Metabolismo (INIGEM, CONICET-UBA), Hospital de Clínicas "José de San -Martín", C1120AAR Buenos Aires, Argentina.
authors.forename: C M
authors.initials: CM
authors.lastname: Rivolta
mesh_terms: D000595:Amino Acid Sequence; D041321:Chromosomes, Human, X / Q000235:genetics; D004247:DNA / Q000737:chemistry; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010375:Pedigree; D011228:Prealbumin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013974:Thyroxine / Q000378:metabolism*; D056825:Thyroxine-Binding Globulin / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics
chemical_list: D011228:Prealbumin; C534944:SERPINA7 protein, human; D056825:Thyroxine-Binding Globulin; D004247:DNA; D013974:Thyroxine