CAJ | 학술논문

目的对20例男性不明原因智力障碍伴癫(癎)患者进行基因筛查,并分析阳性突变携带者的临床特点.方法收集患儿及其父母的血样,提取基因组DNA,采用目标区序列捕获及第2代测序技术进行候选基因检测,采用聚合酶链反应(PCR)直接测序方法对检测出的阳性基因突变进行验证.结果 20例患儿中,3例患儿存在基因突变,阳性率15％,3例患儿基因突变均为X染色体基因错义突变,分别为:OPHN1基因c.1996C＞G,RAB39B基因c.542C＞T及AFF2基因c.427A＞T,此前均未见文献报道.基因功能分析、氨基酸保守性分析、健康人群发生频率检索、生物信息学预测及核心家系遗传方式检测结果均提示3种突变为有害突变,且突变所在基因均为目前已知X连锁智力障碍伴癫(癎)的相关基因,提示上述3种突变是致病突变的可能性大,或至少可以显著增加男性携带者的患病风险.结论 X染色体关键基因突变/功能异常可能是男性智力障碍伴癫(癎)患儿的重要原因之一,未来X染色体智力障碍相关基因检查应作为男性智力障碍伴癫(癎)患儿的重要检查手段.
목적 대20례남성불명원인지력장애반전(간)환자진행기인사사,병분석양성돌변휴대자적림상특점.방법 수집환인급기부모적혈양,제취기인조DNA,채용목표구서렬포획급제2대측서기술진행후선기인검측,채용취합매련반응(PCR)직접측서방법대검측출적양성기인돌변진행험증.결과 20례환인중,3례환인존재기인돌변,양성솔15％,3례환인기인돌변균위X염색체기인착의돌변,분별위:OPHN1기인c.1996C＞G,RAB39B기인c.542C＞T급AFF2기인c.427A＞T,차전균미견문헌보도.기인공능분석、안기산보수성분석、건강인군발생빈솔검색、생물신식학예측급핵심가계유전방식검측결과균제시3충돌변위유해돌변,차돌변소재기인균위목전이지X련쇄지력장애반전(간)적상관기인,제시상술3충돌변시치병돌변적가능성대,혹지소가이현저증가남성휴대자적환병풍험.결론 X염색체관건기인돌변/공능이상가능시남성지력장애반전(간)환인적중요원인지일,미래X염색체지력장애상관기인검사응작위남성지력장애반전(간)환인적중요검사수단.
Objective To detect genetic causes of idiopathic mental retardation/developmental delay in 20 male patients with epilepsy and to analyze their clinical characteristics of positive mutation carriers.Methods The families,consisted of the patient and his parents were recruited.Genomic DNA was extracted from peripheral blood,and candidate gene mutation screening was carried out by next-generation sequencing technology.Mutations in positive gene were verified by polymerase chain reaction(PCR) and direct sequencing.Results Three missense mutations were identified among 3 patients out of 20 cases,with a detection rate of 15％.They were:OPHN1 gene c.1996 C ＞ G,RAB39B gene c.542 C ＞ T and AFF2 gene c.427 A ＞ T,none of which had been reported before.All of these mutations were likely to be pathogenic based on gene function,evolutionary conservation,variant frequency in normal population (NHLBI Exome Sequencing Project and 1 000 Genomes),bioinformatics prediction and inheritance patterns.In addition,all 3 genes disrupted were residing on the X chromosome previously demonstrated to be associated with X-linked mental retardation(XLMR),indicating that they were probably pathogenic or might serve as one of the risk factors.Conclusions Abnormal function of genes on the X chromosomal is one of the most impotent causes of XLMR.X chromosomal gene mutation screening would be recommended for male children suffering from idiopathic mental retardation with epilepsy.