Umeki Kazumi, Yamamoto Ikuo, Yukizane Shigenori, Kotani Tomio
Laboratory for Clinical Investigation, Miyazaki Medical College Hospital, Miyazaki, Japan.
J Pediatr Endocrinol Metab. 2004 Feb;17(2):231-4. doi: 10.1515/jpem.2004.17.2.231.
Thyroid peroxidase (TPO) is a key enzyme of thyroid hormone biosynthesis. TPO abnormality is considered to be a major cause of congenital hypothyroidism (CH) with total iodide organification defect. In the present study, we examined the TPO gene of three siblings, 3 and 2 year-old brothers and a newborn sister, with severe CH. All 17 exons and the promoter region in the TPO gene were directly sequenced using genomic DNA. Two homozygous mutations, C1708T and C2737T, were found in all three patients. The C1708T mutation introduces a premature terminal codon, which is suggested to be a cause of CH. The other mutation, C2737T, and 13 single nucleotide polymorphisms in the patients' TPO genes were also detected as homozygous. We suspect that the mutated alleles were inherited from a single, common ancestor. The haplotype including the two mutations was conserved in a narrow region between D2S2268 and D2S323 microsatellite markers on the end of chromosome 2.
甲状腺过氧化物酶（TPO）是甲状腺激素生物合成的关键酶。TPO异常被认为是导致先天性甲状腺功能减退症（CH）伴全碘有机化缺陷的主要原因。在本研究中，我们检测了三名患有严重CH的兄弟姐妹（分别为3岁和2岁的兄弟以及一名新生儿妹妹）的TPO基因。使用基因组DNA对TPO基因的所有17个外显子和启动子区域进行直接测序。在所有三名患者中均发现了两个纯合突变，即C1708T和C2737T。C1708T突变引入了一个过早的终止密码子，这被认为是CH的一个病因。另外，患者TPO基因中的C2737T突变以及13个单核苷酸多态性也被检测为纯合状态。我们怀疑这些突变等位基因是从一个共同的祖先遗传而来的。包含这两个突变的单倍型在2号染色体末端的D2S2268和D2S323微卫星标记之间的狭窄区域内是保守的。
