Vanvooren V, Uchino S, Duprez L, Costa M J, Vandekerckhove J, Parma J, Vassart G, Dumont J E, Van Sande J, Noguchi S
Institute of Interdisciplinary Research, University of Brussels, Campus Erasme, Route de Lennik 808, B-1070 Brussels, Belgium.
Eur J Endocrinol. 2002 Sep;147(3):287-91. doi: 10.1530/eje.0.1470287.
Constitutively activating mutations of the thyrotropin receptor (TSHR) have been found in the majority of autonomously functioning thyroid nodules (AFTNs) in European patients. The reported frequency of these mutations varies among reports but amounts to 50-80%. To date, only one such mutation responsible for AFTNs has been identified in the Japanese population and the pathogenic role of such mutations in Japanese AFTNs has been questioned. In the present study, we evaluated the frequency of activating mutations in the TSHR and G(alpha)s in 10 Japanese AFTNs.
Genomic DNA was extracted from fresh frozen tissue. The TSHR and the almost entire sequence of the gene coding for the alpha subunit of Gs have been amplified and sequenced.
In sequence analysis, four mutations in the TSHR (T632A, I486M, M453T and L512R) were found. To complete our analysis, we searched mutations in the gene coding for the alpha subunit of Gs, in the samples negative for TSHR mutations. In one case a mutation (R201H) affecting GTPase activity was found.
If we focus on the solitary nodules, we obtain the same mutation proportion as in European patients (70%). The absence of TSHR and G(alpha)s mutations in a significant proportion of autonomous adenomas in multinodular goiters suggests that other causes may also play a role in the genesis of these lesions.
在欧洲患者中，大多数自主功能性甲状腺结节（AFTN）中发现了促甲状腺激素受体（TSHR）的组成性激活突变。这些突变的报告频率在不同报告中有所不同，但达到50%-80%。迄今为止，在日本人群中仅鉴定出一种导致AFTN的此类突变，并且此类突变在日本AFTN中的致病作用受到质疑。在本研究中，我们评估了10个日本AFTN中TSHR和G(α)s激活突变的频率。
从新鲜冷冻组织中提取基因组DNA。对TSHR和编码Gsα亚基的基因的几乎整个序列进行扩增和测序。
在序列分析中，发现TSHR有四个突变（T632A、I486M、M453T和L512R）。为了完成我们的分析，我们在TSHR突变阴性的样本中搜索编码Gsα亚基的基因中的突变。在一个病例中发现了一个影响GTP酶活性的突变（R201H）。
如果我们关注单个结节，我们得到的突变比例与欧洲患者相同（70%）。多结节性甲状腺肿中相当一部分自主性腺瘤不存在TSHR和G(α)s突变，这表明其他原因也可能在这些病变的发生中起作用。
