First report of inherited thyroxine-binding globulin deficiency in Iran caused by a known de novo mutation in SERPINA7

Fahimeh Soheilipour; Hassan Fazilaty; Fatemeh Jesmi; William A Gahl; Babak Behnam

doi:10.1016/j.ymgmr.2016.06.001

First report of inherited thyroxine-binding globulin deficiency in Iran caused by a known de novo mutation in SERPINA7

Mol Genet Metab Rep. 2016 Jun 11:8:13-6. doi: 10.1016/j.ymgmr.2016.06.001. eCollection 2016 Sep.

Authors

Fahimeh Soheilipour¹, Hassan Fazilaty², Fatemeh Jesmi³, William A Gahl⁴, Babak Behnam⁵

Affiliations

¹ Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran.
² Department of Medical Genetics and Molecular Biology, Iran University of Medical Sciences (IUMS), Tehran, Iran.
³ Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, Tehran, Iran.
⁴ NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, MD, USA; Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, MD, USA.
⁵ Department of Medical Genetics and Molecular Biology, Iran University of Medical Sciences (IUMS), Tehran, Iran; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, NIH, Bethesda, MD, USA; Office of the Clinical Director, NHGRI, National Institutes of Health, Bethesda, MD, USA.

Abstract

Background: Thyroxine-binding globulin (TBG) is the main transporter of thyroid hormones in human serum, encoded by the gene TBG (SERPINA7), located in long arm of X-chromosome (Xq21-q22). Deficiency of SERPINA7 (serum protease inhibitor, clade A [alpha-1 antiproteinase, antitrypsin], member 7) leads to inherited TBG deficiency. Several mutations have been reported in the coding and noncoding regions of SERPINA7 in association with TGB deficiency.

Methods: Automated chemiluminescence immunoassays were used to determine TSH, free and total T4 and T3 (fT4, TT4, TT3) and TBG. Direct DNA sequencing identified the mutation in SERPINA7.

Results: We present a 3 and 4/12 year old boy, born premature, who was mismanaged as hypothyroidism before referral to our center, and was diagnosed with TBG deficiency at our center with a hemizygous substitution in exon 1, position c.347T > A, leading to replacement of isoleucine for arginine in position 96 (considering the first 20 amino acid signal peptide).

Conclusion: This known mutation, reported as the first SERPINA7 mutation in Iran, emphasizes the point that endocrinologists should pay more attention to inherited TBG to prevent unnecessary treatment.

Keywords: Iran; Mutation; SERPINA7; TBG.

Publication types

Case Reports