CAJ | 학술논문

目的研究一例儿童Peutz-Jeghers综合征家系的临床特征及其LKB1基因突变.方法收集家系的临床资料,并分别留取家系成员外周血,采用多重连接探针扩增技术、DNA测序分别检测LKB1基因大片段缺失、碱基突变、碱基插入和缺失,同时采用PCR结合变性高效液相色谱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.结果先证者具有典型的皮肤黏膜黑斑、多发胃肠道错构瘤性息肉,先证者及1名家系成员均携带LKB1基因c.924G＞C位点的病理性胚系突变,导致Trp308 Cys的错义突变的发生；这一突变在正常人群中不存在；蛋白质结构和功能分析结果显示Trp308 Cys突变可改变蛋白质的空间构象,进而影响了蛋白质功能.结论 Peutz-Jeghers综合征具有皮肤黏膜色素沉着、胃肠道多发性错构瘤性息肉和家族遗传性三大特征,呈常染色体显性遗传,LKB1基因胚系突变是其致病因素,利用LKB1基因鉴定和突变筛选所有患者及一级亲属对明确诊断及改善其家族的生存期具有重要意义.
목적 연구일례인동Peutz-Jeghers종합정가계적림상특정급기LKB1기인돌변.방법 수집가계적림상자료,병분별류취가계성원외주혈,채용다중련접탐침확증기술、DNA측서분별검측LKB1기인대편단결실、감기돌변、감기삽입화결실,동시채용PCR결합변성고효액상색보사사험증돌변위점재정상인군중적분포.생물신식학분석돌변위점대편마단백질결구화공능적영향.결과 선증자구유전형적피부점막흑반、다발위장도착구류성식육,선증자급1명가계성원균휴대LKB1기인c.924G＞C위점적병이성배계돌변,도치Trp308 Cys적착의돌변적발생；저일돌변재정상인군중불존재；단백질결구화공능분석결과현시Trp308 Cys돌변가개변단백질적공간구상,진이영향료단백질공능.결론 Peutz-Jeghers종합정구유피부점막색소침착、위장도다발성착구류성식육화가족유전성삼대특정,정상염색체현성유전,LKB1기인배계돌변시기치병인소,이용LKB1기인감정화돌변사선소유환자급일급친속대명학진단급개선기가족적생존기구유중요의의.
Objective To investigate clinical characteristics and mutation of the LKB1 gene in a Peutz-Jeghers syndrome (PJS) pedigree.Method Clinical data of a PJS family were analyzed and LKB1 gene mutation was detected by systematic screening with multiplex ligation-dependent probe amplification (MLPA) and DNA sequencing.Meanwhile,two hundred and fifty healthy adults were enrolled in this study and denaturing high performance liquid chromatography (PCR-DHPLC) was carried out to verify the mutation excluding polymorphism sites found in this family.Changes in protein structure and function caused by the mutated coding sequence was analyzed by SWISS-MODEL software.Result The proband had pigmented mucocutaneous lesions and multiple hamartomatous polyps in the gastrointestinal tract.There was no fragment deletion of LKB1 gene detected by MLPA.Among PJS family and 250 healthy adults,germline mutation c.924G ＞ C of LKB1 which cause Trp308Cys in protein sequence was identified only in the proband and another affected member.LKBI protein activity could be reduced due to changes in LKB1 protein conformation structure by Trp308Cys.Conclusion Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterised by mucocutaneous pigmentation,multiple gastrointestinal hamartomatous polyps and heredofamilial nature.Gene identification and mutagen screening of LKB1 gene in all PJS patients and first degree relatives will contribute to a definite diagnosis and improve the life span of the family.