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A 20-basepair duplication in the human thyroid peroxidase gene results in a total iodide organification defect and congenital hypothyroidism

Journal Article · · Journal of Clinical Endocrinology and Metabolism
In this study, the authors present the molecular basis of a total iodide organification defect causing severe congenital hypothyroidism. In the thyroid gland of the patient, thyroid peroxidase (TPO) activity and the iodination degree of thyroglobulin were below detection limits, and no TPO messenger ribonucleic acid was detectable by Northern blot analysis. Denaturing gradient gel electrophoretic analysis of the TPO gene of the patient revealed a homozygous mutation in exon 2. Sequence analysis showed the presence of a 20-basepair duplication, 47 basepairs down-stream of the ATG start codon. This duplication generates a frame shift, resulting in a termination signal in exon 3, compatible with the complete absence of TPO. Both parents of the patient are heterozygous for the same duplication, confirming the recessive mode of inheritance of the mutation. 32 refs., 4 figs.
OSTI ID:
54491
Journal Information:
Journal of Clinical Endocrinology and Metabolism, Journal Name: Journal of Clinical Endocrinology and Metabolism Journal Issue: 1 Vol. 79; ISSN JCEMAZ; ISSN 0021-972X
Country of Publication:
United States
Language:
English

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