PDF(Pubmed)
Abstract：
Peutz-Jeghers syndrome (PJS) is a rare hereditary disorder linked to increased cancer risk due to specific genetic variants in the STK11 gene. This study aimed to assess disease manifestations, genetic profiles, and genotype-phenotype correlations in PJS patients. Twenty patients from 14 families with PJS who were followed up at our clinic between 2011 and 2021 were included. Genetic susceptibility to hereditary cancers was assess-ed using targeted next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) of the STK11 gene. Clinical data were also collected and analyzed in conjunction with the genetic findings. Initial symptoms appeared around 18.9 years, predominantly abdominal pain and intussusception. Mucocutaneous lesions were found in 85%, and hamartomatous polyps in 90%. Dysplastic polyps were found in 4 patients, with 3 cases of malignancy. Nextgeneration sequencing identified 11 pathogenic and 3 likely pathogenic mutations, including 3 novel STK11 variants (LRG_319: c.598- 8_601del, LRG_319: c.708_718del, and LRG_319: c.146_147del). Next-generation sequencing diagnostic rate was 78.5% (11/14), and the overall diagnostic rate with NGS and MLPA studies was 85.7% (12/14). Patients without STK11 mutations had later symptom onset and potentially lower cancer risk. Truncated mutations are associated with earlier symptoms and elevated cancer risk. This is the first PJS case series in Turkey using the NGS and MLPA methods. It reports 3 novel mutations and emphasizes the genotype-phenotype relationship of PJS. With further studies, the genotype-phenotype relationship of STK11 variants will be better understood.
摘要：
Peutz-Jeghers综合征（PJS）是一种罕见的遗传性疾病，由于STK11基因的特定遗传变异而导致癌症风险增加。这项研究旨在评估疾病的表现，遗传概况,和PJS患者的基因型-表型相关性。包括来自14个PJS家庭的20名患者，他们在2011年至2021年期间在我们的诊所进行了随访。使用STK11基因的靶向下一代测序（NGS）和多重连接依赖性探针扩增（MLPA）评估遗传性癌症的遗传易感性。还收集了临床数据并结合遗传发现进行了分析。最初的症状出现在18.9年左右，主要是腹痛和肠套叠。皮肤粘膜病变占85%，错构瘤息肉占90%。在4名患者中发现了增生性息肉，恶性肿瘤3例。下一代测序确定了11个致病性和3个可能的致病性突变，包括3种新颖的STK11变体（LRG_319：c.598-8_601del，LRG_319:c.708_718del,和LRG_319：c.146_147del）。下一代测序诊断率为78.5%(11/14)，NGS和MLPA研究的总诊断率为85.7%(12/14)。没有STK11突变的患者症状发作较晚，可能降低癌症风险。截短的突变与早期症状和癌症风险升高有关。这是土耳其第一个使用NGS和MLPA方法的PJS案例系列。它报道了3个新的突变，并强调了PJS的基因型-表型关系。随着进一步的研究，将更好地理解STK11变异体的基因型-表型关系.
