Large deletions and splicing-site mutations inthe STK11 gene in Peutz-Jeghers Chilean families
Large deletions and splicing-site mutations inthe STK11 gene in Peutz-Jeghers Chilean families
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DOI：
10.1111/j.1399-0004.2012.01928.x
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发表时间：
2013-04-01
影响因子：
3.5
通讯作者：
Alvarez, K.
中科院分区：
文献类型：
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作者：
Orellana, P.;Lopez-Koestner, F.;Alvarez, K.
Peutz-Jeghers综合征（PJS）是一种常染色体显性遗传病，其特征为皮肤粘膜黑素细胞斑，胃肠道错构瘤性息肉病和各种肿瘤的风险增加。丝氨酸/苏氨酸激酶11 （STK11）基因的种系突变已被确定为PJS的一个原因。本研究的目的是表征智利PJS患者的基因型。采用单链构象多态性分析、DNA测序和多重连接依赖探针扩增试验对来自8个PJS家族的13例患者进行突变筛选。通过远程聚合酶链反应和测序来评估基因组重排的断点。结果显示，STK11基因在7个不相关家族中存在7种不同的致病突变，包括3个点突变和4个大基因组缺失。其中三个点突变（43%,3/7）可能被认为是新的。我们的研究结果显示，88%符合PJS诊断标准的先证中存在STK11种系突变。在本研究中，结合两种不同的实验方法筛选PJS中的STK11，导致更高的突变检出率。
Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by mucocutaneous melanocytic macules, gastrointestinal hamartomatous polyposis and an increased risk of various neoplasms. Germline mutations in the serine/threonine kinase 11 (STK11) gene have been identified as a cause for PJS. The aim of this study was to characterize the genotype of Chilean PJS patients. Mutation screening of 13 patients from eight PJS families was performed using a single strand conformation polymorphism analysis, DNA sequencing and multiplex ligation-dependent probe amplification assay. The breakpoints of the genomic rearrangements were assessed by a long-range polymerase chain reaction and sequencing. The results revealed the existence of seven different pathogenic mutations in STK11 gene in seven unrelated families, including three point mutations and four large genomic deletions. Three of these point mutations (43%, 3/7) may be considered as novel. Our results showed that a germline mutation is present in STK11 in 88% of probands fulfilling the diagnostic criteria of PJS. In this study, the combination of two different experimental approaches in the screening of the STK11 in PJS, led to a higher percentage of mutation detection.