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

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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 %).

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          Molecular Cloning : A Laboratory Manual

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            Risk of malignancy in nonpalpable thyroid nodules: predictive value of ultrasound and color-Doppler features.

            The aim of the study was to correlate the sonographic [ultrasound (US)] and color-Doppler (CFD) findings with the results of US-guided fine needle aspiration biopsy (FNA) and of pathologic staging of resected carcinomas to establish: 1) the relative importance of US features as risk factors of malignancy; and 2) a cost-effective management of nonpalpable thyroid nodules. Four hundred ninety-four consecutive patients with nonpalpable thyroid nodules (8-15 mm) were evaluated by US, CFD, and US-FNA. Ninety-two patients with inadequate cytology were excluded from the study. All patients with suspicious or malignant cytology underwent surgery, whereas subjects with benign cytology had clinical and US control 6 months later. Thyroid malignancies were observed in 18 of 195 (9.2%) solitary thyroid nodules and in 13 of 207 (6.3%) multinodular goiters. Cancer prevalence was similar in nodules greater or smaller than 10 mm (9.1 vs. 7.0%). Extracapsular growth (pT(4)) was present in 35.5%, and nodal involvement in 19.4% of neoplastic lesions, with no significant differences between tumors greater or smaller than 10 mm. At US cancers presented a solid hypoechoic appearance in 87% of cases, irregular or blurred margins in 77.4%, an intranodular vascular pattern in 74.2%, and microcalcifications in 29.0%. Irregular margins (RR 16.83), intranodular vascular spots (RR 14.29), and microcalcifications (RR 4.97) were independent risk factors of malignancy. FNA performed on hypoechoic nodules with at least one risk factor was able to identify 87% of the cancers at the expence of cytological evaluation of 38.4% of nonpalpable lesions. The majority of nonpalpable thyroid tumors can be identified by cytological evaluation of lesions presenting hypoechoic appearance in conjunction with one independent risk factor. Due to the nonnegligible prevalence of extracapsular growth and nodal metastasis, US-FNA should be performed on all 8-15 mm hypoechoic nodules with irregular margins, intranodular vascular spots or microcalcifications. Nonpalpable lesions of the thyroid without risk factors should be followed by means of clinical and US evaluation.
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              Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS).

              Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre. By some estimates, the disorder may account for upwards of 10% of hereditary deafness. Previous genetic linkage studies localized the gene to a broad interval on human chromosome 7q22-31.1. Using a positional cloning strategy, we have identified the gene (PDS) mutated in Pendred syndrome and found three apparently deleterious mutations, each segregating with the disease in the respective families in which they occur. PDS produces a transcript of approximately 5 kb that was found to be expressed at significant levels only in the thyroid. The predicted protein, pendrin, is closely related to a number of known sulphate transporters. These studies provide compelling evidence that defects in pendrin cause Pendred syndrome thereby launching a new area of investigation into thyroid physiology, the pathogenesis of congenital deafness and the role of altered sulphate transport in human disease.
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                Author and article information

                Contributors
                alfais2000@yahoo.com
                Journal
                Comp Clin Path
                Comp Clin Path
                Comparative Clinical Pathology
                Springer London (London )
                1618-5641
                1618-565X
                8 August 2012
                8 August 2012
                2014
                : 23
                : 69-75
                Affiliations
                [ ]Genetic Engineering and Biotechnology Institute (GEBI), Baghdad, Iraq
                [ ]Research and Development of Medical Diagnostic Laboratories (CMDL), Al-Razi Centre for Medical Diagnostic kits Production, Ministry of Industry, Baghdad, Iraq
                [ ]Medical College, University of Basrah, Basrah, Iraq
                [ ]Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002 Thailand
                Article
                1572
                10.1007/s00580-012-1572-9
                3890059
                77306339-115e-4a07-b867-23902a6dd057
                © The Author(s) 2012
                History
                : 13 April 2012
                : 18 July 2012
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag London 2014

                Pathology
                thyroid disorders,tpo,c.1708c>t,c.1978c>g,mutation
                Pathology
                thyroid disorders, tpo, c.1708c>t, c.1978c>g, mutation

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