CAJ | 학술논문

目的联合应用多重连接依赖性探针扩增(MLPA)和变性高效液相色谱(DHPLC)技术快速筛查Peutz-Jeghers综合征家系致病基因的突变.方法收集家系成员的外周血,采用MLPA、PCR-DNA测序等方法分别检测了LKB基因大片段缺失、碱基突变、碱基插入和缺失.同时收集250名正常人外周血,PCR-DHPLC筛查验证突变位点在正常人群中的分布.生物信息学分析突变位点对编码蛋白质结构和功能的影响.结果 2名家系受累成员均携带LKB基因924G＞C点的突变,这一突变位点在家系正常人和正常人群中都不存在.突变导致位于功能结构域的第308位编码氨基酸由色氨酸变为半胱氨酸,变异蛋白质结构和功能发生改变.结论 c.924G＞C位点的突变是一种病理性胚系突变,编码氨基酸的改变(Trp308Cys)是此家系的致病性因素.
목적 연합응용다중련접의뢰성탐침확증(MLPA)화변성고효액상색보(DHPLC)기술쾌속사사Peutz-Jeghers종합정가계치병기인적돌변.방법 수집가계성원적외주혈,채용MLPA、PCR-DNA측서등방법분별검측료LKB기인대편단결실、감기돌변、감기삽입화결실.동시수집250명정상인외주혈,PCR-DHPLC사사험증돌변위점재정상인군중적분포.생물신식학분석돌변위점대편마단백질결구화공능적영향.결과 2명가계수루성원균휴대LKB기인924G＞C점적돌변,저일돌변위점재가계정상인화정상인군중도불존재.돌변도치위우공능결구역적제308위편마안기산유색안산변위반광안산,변이단백질결구화공능발생개변.결론 c.924G＞C위점적돌변시일충병이성배계돌변,편마안기산적개변(Trp308Cys)시차가계적치병성인소.
Objective To perform rapid screening of gene mutation by employing multiplex ligationdependent probe amplification(MLPA ) and denaturing high performance liquid chromatography (DHPLC) in a family with Peutz-Jeghers syndrome.Methods Peripheral blood in all the family members was sampled for detection of large fragment deletion,base mutation,base pair insertion and deletion of LKB1 gene by employing MLPA,polymerase chain reaction and DNA sequencing.The peripheral blood in 250 healthy adults was collected for assessment of distribution of mutation points in normal individuals via PCR-DHPLC.Additionally,the impact of mutation points on protein structure and function was assessed by bioinformatics analysis.Results The c.924G＞C point mutation in LKB gene was found in 2 family members and was absent in normal individuals of the family and control population.The gene mutation may result in transformation of tryptophan into eysteine at site 308 in the functional domain leading to altered protein structure and function.Conclusion The c.924G＞C point mutation,pathologically belonging to germline mutation,may be linked to altered protein coding(Trp308Cys).