IDENTIFICATION OF A MUTATION IN THE CODING SEQUENCE OF THE HUMAN THYROID PEROXIDASE GENE CAUSING CONGENITAL GOITER
IDENTIFICATION OF A MUTATION IN THE CODING SEQUENCE OF THE HUMAN THYROID PEROXIDASE GENE CAUSING CONGENITAL GOITER
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DOI：
10.1172/jci115981
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发表时间：
1992-10-01
影响因子：
15.9
通讯作者：
VASSART, G
中科院分区：
文献类型：
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作者：
ABRAMOWICZ, MJ;TARGOVNIK, HM;VASSART, G
甲状腺过氧化物酶（TPO）是合成甲状腺激素的关键酶，TPO缺陷被认为是先天性甲状腺代谢异常的最常见原因。我们调查了一名被收养的碘组织缺陷男孩，他在4个月大时表现为甲状腺功能减退，甲状腺素治疗依从性差，并在12岁时发展为压迫性甲状腺肿，需要部分切除。生化研究显示切除组织中缺乏TPO活性。基因组DNA研究在TPO基因的第8个外显子上发现了一个4个碱基对的插入，并表明该患者是纯合子。这种突变的直接遗传诊断可以通过用NaeI限制性内切酶消化聚合酶链反应产物来进行。这将有助于评估其在TPO缺陷异质遗传群体中的患病率。
Thyroid peroxidase (TPO) is the key enzyme in the synthesis of thyroid hormones, and the TPO defects are believed to be the most prevalent causes of the inborn errors of thyroid metabolism. We investigated an adopted boy with iodide organification defect, who presented with florid hypothyroidism at the age of 4 mo, poorly complied with thyroxine treatment, and developed a compressive goiter necessitating partial resection at the age of 12 yr.Biochemical studies revealed the absence of TPO activity in the resected tissue. Genomic DNA studies identified a 4 base-pair insertion in the eighth exon of the TPO gene, and showed that the patient was homozygous for this frameshift mutation. The direct genetic diagnosis of this mutation can be made by digestion of polymerase chain reaction products with NaeI restriction enzyme. This will help assessing its prevalence among the heterogenous genetic group of TPO defects.