Peutz-Jeghers综合征STK11突变及其与肠套叠累积危险度的关系

STK11 mutation in Peutz-Jeghers syndrome and its relationship with cumulative risk of intussusception

目的分析Peutz-Jeghers综合征(PJS)患者STK11突变及其与肠套叠累积危险度的关系。方法收集2017年12月至2019年6月于空军特色医学中心就诊的167例PJS患者的临床资料,包括患者的性别、年龄、家族史、首次发生肠套叠的年龄和基因检测结果。采用Kaplan-Meier法分析不同突变类型患者肠套叠的累积危险度。统计学方法采用Wilcoxon秩和检验和log-rank检验。结果在167例患者中,89.8%(150/167)的患者发生STK11突变,其中50.7%的突变位点在1、4、5号外显子;70.6%(118/167)的患者发生肠套叠;患者首次发生肠套叠的中位年龄(范围)为15岁(2~52岁)。118例发生肠套叠的PJS患者中,有家族史53例,无家族史65例;男70例,女48例,有无家族史、不同性别PJS患者肠套叠累积危险度的差异均无统计学意义(P均>0.05);STK11突变107例(90.7%)为STK11突变组,STK11未突变11例(9.3%)为STK11未突变组,STK11突变组首次发生肠套叠中位年龄低于STK11未突变组(15岁比31岁),差异有统计学意义(Z=-2.108,P=0.035)。STK11突变组中,无义突变29例(27.1%,无义突变组),框移突变23例(21.5%,框移突变组),错义突变21例(19.6%,错义突变组),剪切突变26例(24.3%,剪切突变组),其他突变类型8例(7.5%)。STK11突变组与STK11未突变组、剪切突变组与STK11未突变组、错义突变组与STK11未突变组间肠套叠的累积危险度的差异均有统计学意义(χ^2=5.570、10.167、6.653,P均<0.05);无义突变组与STK11未突变组、框移突变组与STK11未突变组,以及剪切突变、无义突变、错义突变、框移突变组间肠套叠的累积危险度的差异均无统计学意义(P均>0.05)。结论STK11突变的PJS患者首次发生肠套叠的年龄较小,累积危险度高。STK11突变类型对PJS患者肠套叠的风险评估具有潜在价值。

Objective To analyze the relationship between STK11 mutation and the cumulative risk of intussusception in patients with Peutz-Jeghers syndrome(PJS).Methods From December 2017 to June 2019,the clinical data of 167 patients with PJS in Air Force Medical Center were collected,including gender,age,family history,age of first intussusception and results of gene test.Kaplan-Meier was used to analyze the cumulative risk of intussusception in patients with different mutation types.Wilcoxon rank sum test and log-rank test were used for statistical analysis.Results Among 167 patients,89.8%patients(150/167)had STK11 mutation,and 50.7%of the mutation sites were found in exons 1,exon 4 and exon 5.And 70.6%patients(118/167)developed intussusception.The median age of patients with intussusception for the first time was 15 years(ranged from 2 to 52 years).Among 118 PJS patients with intussusception,53 patients had family history and 65 patients had no family history;70 cases were male and 48 cases were female.There were no statistically significant differences in the cumulative risk of intussusception between PJS patients with and without family history,and between male and female PJS patients(both P>0.05).There were 107 cases(90.7%)with STK11 mutation(STK11 mutation group)and 11 cases(9.3%)without STK11 mutation(STK11 non-mutation group).The median age of first intussusception of STK11 gene mutation group was younger than that of STK11 non-mutation group,and the difference was statistically significant(Z=-2.108,P=0.035).In STK11 mutation group,29 cases(27.1%)were nonsense mutations(nonsense mutation group),23 cases(21.5%)were frameshift mutations(frameshift mutation group),21 cases(19.6%)were missense mutations(missense mutation group),26 cases(24.3%)were splicing mutations(splicing mutation group)and 8 cases(7.5%)of other mutations.There were statistically significant differences in the cumulative risk of intussusception between the STK11 mutation group and the STK11 non-mutation group,the STK11 splicing mutation group and the STK11 non-mutation group,STK11 missense mutation group and the STK11 non-mutation group(χ^2=5.570,10.167 and 6.653,all P<0.05).There were no statistically significant differences in the cumulative risk of intussusception between STK11 nonsense mutation group and STK11 non-mutation group,between STK11 frame-shift mutation group and STK11 non-mutation group,among groups with different mutation types of STK11 gene(all P>0.05).Conclusions The younger the age of first intussusception in PJS patients with STK11 mutation,the higher the cumulative risk.The mutation type of STK11 gene has potential value for the risk assessment of intussusception in PJS patients.