MECP2重复综合征的家系分子遗传学分析及产前诊断  

Molecular genetic analysis and prenatal diagnosis of methyl-CpG-binding protein 2 duplication syndrome’s pedigree

作　　者：刘芙蓉[1] 王兴[1] 郝胜菊[1] 张庆华[1] 马盼盼 张钏[1] 周秉博 LIU Furong;WANG Xing;HAO Shengju;ZHANG Qinghua;MA Panpan;ZHANG Chuan;ZHOU Bingbo(Gansu Provincial Maternity and Child-care Hospital,Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases,Lanzhou,Gansu 730050,China)

机构地区：[1]甘肃省妇幼保健院医学遗传学中心/甘肃省出生缺陷与罕见病临床研究中心,甘肃兰州730050

出　　处：《中国优生与遗传杂志》2022年第7期1240-1244,共5页Chinese Journal of Birth Health & Heredity

基　　金：甘肃省卫生健康行业科研项目(GSWSKY2020-39)。

摘　　要：目的 探讨MECP2重复综合征(MDS)的临床特征及分子遗传学特点,对该病患者进行家系分析及产前诊断,利用多种检测技术联合验证,提高对此类疾病的诊断能力。方法 采集患儿、患儿姐姐及其父母外周血行淋巴细胞染色体核型分析,患儿母亲再次妊娠,其母羊水行羊水染色体核型分析及高通量测序染色体组拷贝数分析(CNVs),患儿及胎儿通过CNVs精确定位拷贝数异常改变的染色体片段区域,多重连接探针扩增技术(MLPA)验证CNVs结果并进行家系分析。结果 患儿特殊面容、智力障碍、语言缺失、反复呼吸道感染,肌张力低下。患儿、胎儿及其家系成员染色体核型未见明显异常。CNVs检出患儿在Xq28区域重复0.28 Mb,胎儿在相同位置重复0.46 Mb,此区域包含MECP2等重要功能基因,为临床致病型拷贝数变异,确诊为MDS;MLPA验证患儿及胎儿MECP2及IRAK1基因重复,确定患儿母亲及姐姐为MECP2基因重复的携带者,女性携带者均无异常临床表现。患儿父亲正常。结论 结合临床特征、CNVs及MLPA技术可有效对MDS进行家系分析及产前诊断。Objective The aim of this research is to to explore the clinical and molecular genetic characteristics of MECP2 duplication syndrome(MDS). Carrying out family analysis and prenatal diagnosis of patients with this disease. Using a variety of testing techniques to verify it. Improving the diagnostic capabilities of such diseases. Methods To collect the child,his sister and their parents for the lymphocyte nucleotype analysis. Amniotic fluid chromosome karyotype analysis and copy number variation analysis(CNVs) was carried out to the fetus. Precisely locating the chromosome fragment regions with abnormal copy number changes. Multiple ligation probe amplification technology(MLPA) was used to confirm the results and perform family analysis. Results The child with special facial features, mental retardation, language loss, repeated respiratory infections, and hypotonia. The chromosomal karyotypes of the child, fetus and their family members were normal. CNVs detected a duplication of 0.28 Mb in the Xq28 region with the child, a duplication of 0.46 Mb at the same position with the fetus. This region contains important functional genes such as MECP2, which is a clinically pathogenic copy number variation.Diagnosed as MDS. MLPA verified the MECP2 and IRAK1 gene duplication in child and fetus. Confirmed their mother and sister were carriers of the MECP2 gene duplication, there were no abnormal clinical manifestations in female carriers. The father of the child is normal. Conclusion Combining clinical features, CNVs and MLPA technology can effectively perform family analysis and prenatal diagnosis of MDS.

关 键 词：MECP2重复综合征(MDS) 高通量测序染色体组拷贝数变异分析 多重连接探针扩增技术 产前诊断 

分 类 号：R725.9[医药卫生—儿科]