Detection of heterozygous c.1708C&gt;T and c.1978C&gt;G thyroid peroxidase (TPO) mutations in Iraqi patients with toxic and nontoxic goiter

A H M Al-Faisal,I J Al-Ramahi,A T Hamdan,S Barusrux,I A Abudl-Hassan

doi:10.1007/s00580-012-1572-9

Detection of heterozygous c.1708C>T and c.1978C>G thyroid peroxidase (TPO) mutations in Iraqi patients with toxic and nontoxic goiter

A H M Al-Faisal, I J Al-Ramahi + Show 3 more

Open Access

https://doi.org/10.1007/s00580-012-1572-9

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Abstract

Sixty-three Arabic patients (16 males and 47 females) with thyroid toxic and nontoxic goiter who attended the endocrinologist in Nuclear Medicine Hospital and Al Yarmok Nuclear Medicine Department in Baghdad, Iraq were examined for thyroid peroxidase (TPO) gene mutations. A total of ten heterozygous mutations have been identified in the human TPO gene associated with thyroid toxic and nontoxic goiter. These mutations involved transition or transversion of cysteine either by thymine or guanine at the position 1708 of the exon 10 (c.1708C>T) and the position 1978 of the exon 11 (c.1978C>G). From a total of ten detected mutations, two c.1978C>G mutations were detected in nontoxic goiter patients and eight (two c.1708C>T and six c.1978C>G mutations) were detected in toxic goiter. In conclusion, this study identified ten TPO mutations associated with toxic and nontoxic goiter that have not been yet reported in Iraq, and most of them are detected among females (90 %) and adults age between 30 and 50 years old (80 %).

Highlights

Thyroid peroxidase (TPO) enzyme is a thyroid-specific glycosylated hemoprotein with a short transmembrane domain that binds it to the apical membrane of the thyrocyte (Park and Chatterjee 2005), with the catalytic part facing inside the follicle
Published molecular genetic studies suggest that TPO gene mutations are one of the most common causes of thyroid dyshormonogenesis, with several different inactivating mutations being identified in patients with total iodide organification defects (Yardena et al 2007)
No TPO mutations were detected in healthy samples

Summary

Introduction

Thyroid peroxidase (TPO) enzyme is a thyroid-specific glycosylated hemoprotein with a short transmembrane domain that binds it to the apical membrane of the thyrocyte (Park and Chatterjee 2005), with the catalytic part facing inside the follicle. It consists of 933 amino acids that are encoded by an mRNA of 3,048 nucleotides (Park and Chatterjee 2005). More than 50 TPO gene mutations have been identified including deletion, insertion, or change in DNA building blocks (Hamosh et al 2005) Some of these mutations led to an abnormally thyroid peroxidase enzyme that breaks apart before it can be inserted into the cell membrane. Other mutations change the enzyme's three-dimensional shape, preventing it from functioning properly within the cell membrane and causing the nonaddition of the functional thyroid peroxidase iodine taken up by the thyroid gland to thyroglobulin (Avbelj et al 2007; Yardena et al 2007; Deladoe et al 2008)

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