Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour syndrome
Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour syndrome
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DOI：
10.1111/j.1365-2796.2004.01421.x
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发表时间：
2005-01-01
影响因子：
11.1
通讯作者：
Thakker, RV
中科院分区：
文献类型：
--
作者：
Bradley, KJ;Hobbs, MR;Thakker, RV
高甲状旁腺-颌肿瘤（HPT-JT）综合征是一种常染色体显性遗传疾病，以甲状旁腺肿瘤为特征，常为癌。和骨化性颌骨纤维瘤此外，一些患者可能会发展为肾肿瘤和囊肿。引起HPT-JT的基因，被称为HRPT 2，位于染色体1q31.2上。编码531个氨基酸的蛋白质，称为副纤维蛋白。到目前为止，有42个突变，其中22个是种系突变。已经报道，其中97%是失活的，与HRPT 2的肿瘤抑制作用一致。我们调查了另外四个HPT-JT家族的生殖系突变，寻找其他临床表型，并检查其基因型-表型相关性。在两个家庭中发现了突变。一个家族在密码子669处有一个新的缺失插入，另一个在密码子679处有一个2 bp的插入，这在其他四个无关的患者中已有报道。这五个不相关的患者和他们的家庭具有相同的突变没有发现发展相同的肿瘤，从而表明基因型-表型相关性的缺乏。对33个HPT-JT家系的分析显示，13个HPT-JT家系中的受影响妇女在其第二至第四个十年中遭受月经过多。这通常需要进行子宫切除术，这表明存在子宫肿瘤。这大大减少了艾滋病的母婴传播。因此，我们的分析结果扩大了HPT-JT相关肿瘤的范围，包括子宫肿瘤，这些可能是HPT-JT家族女性生殖健康下降的原因。
The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterized by parathyroid tumours, which are frequently carcinomas. and ossifying jaw fibromas. In addition, some patients may develop renal tumours and cysts. The gene causing HPT-JT, which is referred to as HRPT2 and is located on chrornosome 1q31.2. encodes a 531 amino acid protein called PARAFIBROMIN. To date 42 mutations, of which 22 are germline. have been reported and 97% of these are inactivating and consistent with a tumour suppressor role for HRPT2. We have investigated another four HPT-JT families for germline mutations, searched for additional clinical phenotypes, and examined for it genotype-phenotype correlation. Mutations were found in two families. One family had a novel deletional-insertion at codon 669, and the other had a 2 bp insertion at codon 679, which has been reported in four other unrelated patients. These five unrelated patients and their families with the same mutation were not found to develop the same tumours, thereby indicating an absence of a genotype-phenotype correlation. An analysis of 33 HPT-JT kindreds revealed that affected women in 13 HPT-JT families suffered from menorrhagia in their second to fourth decades. This often required hysterectomy, which revealed the presence of uterine tumours. This resulted in a significantly reduced maternal transmission of the disease. Thus, the results of Our analysis expand the spectrum of HPT-JT-associated tumours to include uterine tumours, and these may account for the decreased reproductive fitness in females from HPT-JT families.