Thyroperoxidase Gene Mutations in Congenital Goitrous Hypothyroidism with Total and Partial Iodide Organification Defect
| Autor: | Dulce R. Guedes, Geraldo Medeiros-Neto, Cecília L. S. Santos, Ileana G.S. Rubio, Meyer Knobel, Antonio C. do Nascimento |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Heterozygote medicine.medical_specialty Adolescent Potassium Compounds Endocrinology Diabetes and Metabolism Thyroid Gland Genes Recessive Gene mutation Compound heterozygosity medicine.disease_cause Iodide Peroxidase Exon Endocrinology Hypothyroidism Thyroid peroxidase Internal medicine Congenital Hypothyroidism Humans Medicine Genetic Testing Mutation Perchlorates Polymorphism Genetic Base Sequence Flavoproteins biology Goiter business.industry Homozygote Thyroid NADPH Oxidases Organification Iodides medicine.disease Dual Oxidases Congenital hypothyroidism medicine.anatomical_structure DNA Transposable Elements biology.protein business |
| Zdroj: | Thyroid. 13:1145-1151 |
| ISSN: | 1557-9077 1050-7256 |
| Popis: | Mutations of the thyroperoxidase (TPO) gene have been reported as being the most severe and frequent abnormality in thyroid iodide organification defect (IOD) causing goitrous congenital hypothyroidism. The objective of this study was to screen and subsequently identify TPO gene mutations in patients with congenital hypothyroidism with evidence of total iodine organification defects (TIOD) or partial iodine organification defect (PIOD) as defined by the perchlorate discharge test. Seven goitrous patients with TIOD and seven patients with PIOD, from three and five unrelated families, respectively, were studied. We were able to detect different TPO genes mutations in patients with TIOD and PIOD. In TIOD families the results were as follows: (1) a homozygous GGCC insertion at exon 8, position 1277 (family 1); (2) compound heterozygosity with a GGCC insertion at exon 8 (1277) and a nucleotide substitution in exon 11 (2068GC) (family 2); (3) compound heterozygosity with the mutation 2068GC in exon 11 and a C insertion in exon 14 between positions 2505-2511 (family 3). In patients with PIOD we have detected: (1) only one heterozygous mutation in two families (4 and 5), in exons 11 and 10 (2084GA and 1780CA); (2) a compound heterozygous condition in one family (family 6), with mutations, respectively in exons 8 and 10 (1242GT and 1780CA); (3) only polymorphisms (family VII) and (4) a heterozygous mutation in the first base of the border exon/intron 9 +1GT (family VIII). We did not detect inactivating mutations in exons 11, 16, and 21 of the THOX2 gene where mutations have been previously described. We concluded that homozygous and compound heterozygous mutations found in TIOD characterized the autosomal recessive mode of inheritance and will translate a nonfunctional protein or a protein that may not reach the apical membrane. As for PIOD, the majority of the studied kindreds had only heterozygous mutations and/or polymorphisms. It is conceivable that these TPO gene sequence alterations may partially affect the functional state of the translated protein or affect its transport to the apical membrane. |
| Databáze: | OpenAIRE |
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