CAJ | 학술논문

目的探讨SMN1、SMN2、NAIP、GTF2H2及H4F5基因拷贝数与脊髓性肌萎缩症(spinal muscular atrophy,SMA)患儿临床分型的关系,评估四川地区孕妇运动神经元存活基因(survival motor neuron,SMN)拷贝数情况及携带者筛查.方法应用多重连接依赖探针扩增技术(multiplex ligationdependent probe amplification,MLPA)对确诊的53例SMA患者SMN1、SMN2、NAIP、GTF2H2和H4F5基因拷贝数进行检测,用Fisher精确检验法对SMA临床分型与SMN1基因拷贝数进行统计分析,同时应用变性高效液相色谱分析技术(denaturing high performance liquid chromatography,DHPLC)对四川地区427名孕妇SMN1基因第7外显子进行缺失筛查.结果 53例SMA患者中Ⅰ型、Ⅱ型和Ⅲ型的SMN1基因第7和8外显子均纯合缺失的比例分别为100％、94.44％和87.50％,仅第7外显子纯合缺失的比例分别为0、5.56％和12.50％;SMN2第7外显子拷贝数为1、2、3和4拷贝的比例分别为11.32％、67.92％、13.21％和7.55％;NAIP第5外显子拷贝数为0、1和2拷贝的患者分别为11.32％,62.26％和26.42％.未检测到GTF2H2和H4F5基因缺失.SMN1基因第7外显子在四川地区孕妇人群的杂合缺失率为2.11％.结论 SMA患者的临床分型与SMN2基因和NA IP基因拷贝数有关(P＜0.05),而与SMN1基因第7和8外显子缺失模式无关联(P＞0.05).通过检测SMN1的拷贝数可辅助筛查SMA携带者.对无SMA家族史的普通群体进行SMA致病基因携带筛查时,应考虑“2+0”型携带者对筛查结果的影响,谨慎地解释筛查结果.
목적 탐토SMN1、SMN2、NAIP、GTF2H2급H4F5기인고패수여척수성기위축증(spinal muscular atrophy,SMA)환인림상분형적관계,평고사천지구잉부운동신경원존활기인(survival motor neuron,SMN)고패수정황급휴대자사사.방법 응용다중련접의뢰탐침확증기술(multiplex ligationdependent probe amplification,MLPA)대학진적53례SMA환자SMN1、SMN2、NAIP、GTF2H2화H4F5기인고패수진행검측,용Fisher정학검험법대SMA림상분형여SMN1기인고패수진행통계분석,동시응용변성고효액상색보분석기술(denaturing high performance liquid chromatography,DHPLC)대사천지구427명잉부SMN1기인제7외현자진행결실사사.결과 53례SMA환자중Ⅰ형、Ⅱ형화Ⅲ형적SMN1기인제7화8외현자균순합결실적비례분별위100％、94.44％화87.50％,부제7외현자순합결실적비례분별위0、5.56％화12.50％;SMN2제7외현자고패수위1、2、3화4고패적비례분별위11.32％、67.92％、13.21％화7.55％;NAIP제5외현자고패수위0、1화2고패적환자분별위11.32％,62.26％화26.42％.미검측도GTF2H2화H4F5기인결실.SMN1기인제7외현자재사천지구잉부인군적잡합결실솔위2.11％.결론 SMA환자적림상분형여SMN2기인화NA IP기인고패수유관(P＜0.05),이여SMN1기인제7화8외현자결실모식무관련(P＞0.05).통과검측SMN1적고패수가보조사사SMA휴대자.대무SMA가족사적보통군체진행SMA치병기인휴대사사시,응고필“2+0”형휴대자대사사결과적영향,근신지해석사사결과.
Objective To assess the association of copy number variations of SMN1,SMN2,NAIP,GTF2H2 and H4F5 genes with clinical classification of spinal muscular atrophy in children,and determine the copy number of the SMN gene among pregnant women.A carrier screening was also performed in Sichuan province.Methods The copy number variations of the above genes among 53 confirmed SMA patients were determined with MLPA technique.The copy number variations were analyzed by the Fisher's exact test.Deletion of exon 7 in the SMN1 gene was screened with denaturing high performance liquid chromatography (DHPLC) for 427 pregnant women.Results Among the 53 cases of type Ⅰ,Ⅱ,and Ⅲ SMA patients,the rate of homozygous deletion of both exons 7 and 8 of the SMN1 gene were 100％,94.44 ％ and 87.50％,respectively,whereas those of homozygous deletion of exon 7 of SMN1 gene were 0,5.56％,and 12.50％,respectively.The patients with 1,2,3,and 4 copies of exon 7 of the SMN2 gene were 11.32％,67.92％,13.21％ and 7.55％,respectively.The patients with 0,1,and 2 copies of exon 5 of NAIP gene were 11.32％,62.26％,and 26.42％,respectively.No deletion was detected in GTF2H2 or H4F5 genes.The heterozygous loss rate of exon 7 in SMN gene in the pregnant women population of Sichuan region was approximately 2.11 ％.Conclusion Copy number variations of SMN2 and NAIP genes in patients are related to SMA clinical types (P＜0.05).In contrast,there was no relationship between SMA clinical types and deletion of exons 7 and 8 in theSMN1 gene (P＞ 0.05).Analysis of copy number change in SMN1 gene can assist SMA carrier screening.However,when the general population without SMA family history is screened for disease-causing genes,it should be noted that the type “2+ 0” carriers may affect the screening result,and the result should be interpreted with caution.