Novel PTEN mutations in patients with Cowden disease:: absence of clear genotype-phenotype correlations
Novel PTEN mutations in patients with Cowden disease:: absence of clear genotype-phenotype correlations
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DOI：
10.1038/sj.ejhg.5200289
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发表时间：
1999-04-01
影响因子：
5.2
通讯作者：
Padberg, GW
中科院分区：
文献类型：
--
作者：
Nelen, MR;Kremer, H;Padberg, GW
考登病 (CD) 的特征是多种组织中存在多发性错构瘤。病理特征是存在许多外毛根瘤。一些神经系统症状也是 CD 的一部分，其中巨脑畸形和 Lhermitte-Duclos 病 (LDD) 是最重要的特征。由于患恶性肿瘤的风险增加，早期识别克罗恩病患者非常重要。乳腺癌是最常见的恶性肿瘤，但泌尿生殖系统癌、消化道癌和甲状腺癌的发病率也较高。 CD 定位于染色体 10q23，并且 PTEN 基因（也称为 MMAC1 或 TEP1）被证明参与其中。在家族性和散发性 CD 患者中均发现了种系突变。我们在 13 名 CD 患者中发现了 8 种 PTEN 突变，其中 7 种是新突变。结合之前的数据，我们确定了 17 个独立的 CD 突变。没有检测到 CD 患者的总体 DNA 改变。讨论了基因型-表型关系。唯一存在的相关性是 LDD 患者中未检测到错义突变。然而，需要更多的数字来证实这一点。早期研究中发现的 PTEN 突变与恶性乳腺疾病发生之间的关联无法得到证实。五名编码序列不带 PTEN 突变的 CD 患者的临床特征与具有 PTEN 突变的 CD 患者没有差异。此外，我们很可能已经识别出荷兰的大多数克罗恩病患者。由此我们估计，CD 在荷兰人群中的患病率约为 25 万分之一，且突变频率较低。
Cowden disease (CD) is characterised by multiple hamartomas in a variety of tissues. The pathological hallmark is the presence of a number of trichilemmomas. Several neurological symptoms are also part of CD with megalencephaly and Lhermitte-Duclos disease (LDD) as the most important features. Early recognition of CD patients is important because of the increased risk of developing malignancies. Breast cancer is the most frequent malignancy, but also urogenital, digestive tract, and thyroid cancers are found,vith higher frequencies. CD was localised to chromosome 10q23 and the PTEN gene (also known as MMAC1 or TEP1) was shown to be involved. Germline mutations were identified in both familial and sporadic CD patients. We identified eight PTEN mutations, of which seven were novel, in 13 CD patients. Combined with previous data we have identified 17 independent CD mutations. Gross DNA alterations in CD patients were not detected. Genotype-phenotype relations are discussed. The only correlation suggested to exist is that missense mutations are not detected in LDD patients. However, larger numbers are needed to confirm this. Association of PTEN mutations and the occurrence of malignant breast disease found in an earlier study cannot be confirmed. Clinical features of five CD patients without a PTEN mutation in the coding sequence do not differ from CD patients with a PTEN mutation. Furthermore, if is likely that we have identified the majority of CD patients in the Netherlands. From this we estimate that CD has a prevalence of about 1 in 250 000 in the Dutch population with a low mutation frequency.