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

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) i...

Full description

Saved in:

Bibliographic Details
Published in:	Hormone and metabolic research Vol. 46; no. 2; p. 100
Main Authors:	Sklate, R T, Olcese, M C, Maccallini, G C, Sarmiento, R G, Targovnik, H M, Rivolta, C M
Format:	Journal Article
Language:	English
Published:	Germany 01-02-2014
Subjects:	Amino Acid Sequence Chromosomes, Human, X - genetics DNA - chemistry Female Genetic Diseases, X-Linked - genetics Humans Male Middle Aged Mutation - genetics Mutation, Missense - genetics Pedigree Prealbumin - chemistry Prealbumin - genetics Prealbumin - metabolism Sequence Alignment Sequence Analysis, DNA Thyroxine - metabolism Thyroxine-Binding Globulin - chemistry Thyroxine-Binding Globulin - deficiency Thyroxine-Binding Globulin - genetics
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
ISSN:	1439-4286
DOI:	10.1055/s-0033-1358741