一个Lubs X-连锁智力障碍综合征家系的分子诊断和功能研究  

Molecular diagnosis and functional study of a pedigree affected with Lubs X-linked mental retardation syndrome

作　　者：江琛[1] 庞楠 吕卫刚[1] 彭莹[1] 刘静[1] 郭若兰 常家祯 梁德生[1] 邬玲仟[1] Jicing Chen;Pang Nan;Lyu Wei gang;Peng Ying;Liu Jing;Guo Ruolan;Chang Jiazhen;Liang Desheng;Wu Lingqian(Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410008, China)

机构地区：[1]中南大学医学遗传学研究中心,长沙410008

出　　处：《中华医学遗传学杂志》2019年第4期340-343,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81501268,81571450);湖南省重点研发计划项目(2016WK2029).

摘　　要：目的确定一个X连锁智力低下家系的遗传学病因。方法对中南大学医学遗传学研究中心收集的一个X连锁隐性遗传的智力障碍家系先证者进行染色体核型分析、FMR1突变检测、基因芯片染色体拷贝数变异分析,并就先证者的拷贝数重复区域在家系成员中行多重连接探针扩增技术(multiplex ligation-dependent probe amplification, MLPA)检测,对先证者拷贝数重复区域包含的基因进行表达分析。结果该家系先证者染色体核型未见异常,FMR1未见致病变异,基因芯片检测发现Xq28区域(ChrX:153 027 633~153 398 515)存在一个370 kb的重复。MLPA确定该重复在家系内与疾病表型共分离,并确定女性携带者。该区域包含MECP2在内的14个基因。在先证者的外周血有核细胞中,重复基因表达上调1.79~5.38倍。结论该家系确诊为Lubs X-连锁智力障碍综合征,受累基因拷贝数增加导致的剂量效应可能是发病的主要原因,根据遗传学诊断结果可以对其家系后代进行遗传咨询和产前诊断。Objective To explore the genetic basis for a pedigree affected with X-linked mental retardation. Methods The proband was subjected to chromosomal karyotyping, FMR1 mutation testing and copy number variation analysis with a single nucleotide polymorphism microarray (SNP array). His family members were subjected to multiplex ligation-dependent probe amplification (MLPA) assaying. Expression of genes within the repeated region were analyzed. Results The proband had a normal chromosomal karyotype and normal number of CGG repeats within the FMR1 gene. SNP array identified a 370 kb duplication in Xq28 (ChrX: 153 027 633- 153 398 515), which encompassed 14 genes including MECP2. The patient was diagnosed as Lubs X-linked mental retardation syndrome (MRXSL). MLPA confirmed the presence of copy number variation, its co-segregation with the disease, in addition with the carrier status of females. Genes from the duplicated region showed higher levels of expression (1.79 to 5.38 folds) within peripheral blood nucleated cells of the proband. Conclusion The patients were diagnosed with MRXSL. The expression of affected genes was up-regulated due to the duplication. Genetic counseling and prenatal diagnosis can be provided based on the results.

关 键 词：X连锁智力低下 Lubs X-连锁智力障碍综合征 MECP2基因 剂量效应 

分 类 号：R596[医药卫生—内科学] R440[医药卫生—临床医学]