Mutations in STK11 gene in Czech Peutz-Jeghers patients.
Mutations in STK11 gene in Czech Peutz-Jeghers patients.
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DOI：
10.1186/1471-2350-10-69
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发表时间：
2009-07-19
影响因子：
--
通讯作者：
Krepelová A
中科院分区：
文献类型：
--
作者：
Vasovcák P;Puchmajerová A;Roubalík J;Krepelová A
Peutz-Jeghers综合征(PJS)是一种常染色体显性遗传性疾病，以皮肤粘膜色素沉着和胃肠道错构瘤性息肉病为特征。丝氨酸/苏氨酸激酶11(STK11)基因的种系突变已被证明与该病有关。患有PJS的个体患各种肿瘤的风险增加。本研究的目的是确定捷克PJS患者的基因型别和表型。我们对来自捷克5个家系的8个个体的基因组DNA进行了测序分析，包括STK11基因启动子区域、整个编码区和剪接点的边界，并采用多重连接依赖的探针扩增(MLPA)方法来鉴定STK11基因的大的外显子缺失或复制。我们在两个符合PJS诊断标准的家系中发现了STK11基因的致病突变，在三个散发性病例中发现了一个不符合诊断标准的病例。携带STK11基因移码突变的患者发生了侵袭性胃癌。到目前为止，还没有其他被研究的先证者患上癌症。结果表明，不仅在符合PJS诊断标准的先证者中可以发现STK11基因的胚系突变，而且在一些不符合PJS诊断标准的散发病例中也可以发现STK11基因的胚系突变。此外，我们观察到一例新的侵袭性胃癌的年轻患者的STK11基因移码突变。
Peutz-Jeghers syndrome (PJS) is an autosomal dominant hereditary disease characterized by mucocutaneous pigmentation and gastrointestinal hamartomatous polyposis. The germline mutations in the serine/threonine kinase 11 (STK11) gene have been shown to be associated with the disease. Individuals with PJS are at increased risk for development of various neoplasms. The aim of the present study was to characterize the genotype and phenotype of Czech patients with PJS. We examined genomic DNA of 8 individuals from five Czech families by sequencing analysis of STK11 gene, covering its promotor region, the entire coding region and the splice-site boundaries, and by multiplex ligation-dependent probe amplification (MLPA) assay designed for the identification of large exonic deletions or duplications of STK11 gene. We found pathogenic mutations in STK11 gene in two families fulfilling the diagnostic criteria of PJS and in one of three sporadic cases not complying with the criteria. The patient with the frameshift mutation in STK11 gene developed aggressive gastric cancer. No other studied proband has developed a carcinoma so far. Our results showed that a germline mutation of STK11 gene can be found not only in probands fulfilling the PJS diagnostic criteria, but also in some sporadic cases not complying with the criteria. Moreover, we observed a new case of aggressive gastric cancer in a young patient with a frameshift mutation of STK11 gene.
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STK11/LKB1的预测启动子元素的序列变化不太可能导致Peutz-Jeghers综合征。
影响因子：
4.4
作者：
Hearle, Nicholas C M;Tomlinson, Ian;Lim, Wendy;Murday, Victoria;Swarbrick, Edwin;Lim, Guan;Phillips, Robin;Lee, Peter;O'Donohue, John;Trembath, Richard C;Morrison, Patrick J;Norman, Andrew;Taylor, Rohan;Hodgson, Shirley;Lucassen, Anneke;Houlston, Richard S
通讯作者：
Houlston, Richard S
影响因子：
29.4
作者：
FOLEY, TR;MCGARRITY, TJ;ABT, AB
通讯作者：
ABT, AB
影响因子：
4
作者：
Hearle, NCM;Rudd, MF;Houlston, RS
通讯作者：
Houlston, RS
影响因子：
24.5
作者：
COCHET, B;CARREL, J;WIDGREN, S
通讯作者：
WIDGREN, S
影响因子：
3.9
作者：
Li, Lili;McVety, Susan;Foulkes, William D
通讯作者：
Foulkes, William D