Prader⁃Willi综合征及Angelman综合征的遗传学分析方案及广东的临床实践  

Genetic analysis program and application of Prader⁃Willi syndrome and Angelman syndrome

作　　者：汪安石[1] 刘畅[1] 王继成[1] 黄演林[1] 张彦[1] 丁红珂[1] 刘玲[1] 杨杰[2] 吴菁[1] 尹爱华[1] WANG Anshi;LIU Chang;WANG Jicheng;HUANG Yanlin;ZHANG Yan;DING Hongke;LIU Ling;YANG Jie;WU Jing;YIN Aihua(Medical Genetic Center,Guangdong Women and Children Hospital,Guangzhou,Guangdong,China,511400;Neonatal Department,Guangdong Women and Children Hospital,Guangzhou,Guangdong,China,511400)

机构地区：[1]广东省妇幼保健院医学遗传中心,广东广州511400 [2]广东省妇幼保健院新生儿科,广东广州511400

出　　处：《分子诊断与治疗杂志》2020年第5期570-574,共5页Journal of Molecular Diagnostics and Therapy

基　　金：广东省医学科学技术研究基金项目(A2019358)。

摘　　要：目的建立Prader⁃Willi综合征(PWS)及Angelman综合征(AS)的遗传学分析方案,应用于广东地区的临床诊疗实践。方法该方案以甲基化特异性PCR作为初筛方法,对1038例样本进行检测,并以STR家系连锁分析法对39例PWS及15例AS阳性病例进行分子致病机制探究。以UBE3A序列分析作为AS分子诊断的补充,对4例AS疑似病例进行检测。通过染色体微阵列分析进一步明确21个确诊病例的染色体断裂位点,并对59例具有类似临床表现的病例进行鉴别诊断。结果应用该遗传分析方案,在广东地区确诊了39例PWS患儿及15例AS患儿。以STR连锁分析法进行分子致病机制探究,发现32例为缺失型PWS、7例母源单亲二倍体型PWS、14例为缺失型AS、1例父源单亲二倍体型AS。序列分析未检出UBE3A基因突变型AS。染色体微阵列分析进一步明确了染色体断裂位点,并另外检出6例与PWS/AS具有表型重叠的染色体微缺失/微重复综合征。结论本研究建立了一种PWS及AS的遗传学分析方案,将PWS及AS患者的确诊年龄显著降低,并确定分子缺陷类型,及早开展干预治疗,有助于改善患儿预后。Objective To establish a genetic analysis program for Prader⁃Willi syndrome(PWS)and Angelman syndrome(AS),and to applyto clinical diagnosis and treatment practice in Guangdong.Methods In this program,methylation⁃specific PCR was used as the initial screening method,and the molecular pathogenic mechanism of PWS and AS positive cases was explored by STR pedigree linkage analysis.UBE3A sequence analysis was used as a supplement to AS molecular diagnosis.The chromosomal microarray analysis was employed to identify chromosomal breakpoints in confirmed cases,and to detect other chromosomal abnormalities in undiagnosed cases.Results Using this genetic analysis protocol,39 children with PWS and 15 children with AS were diagnosed in Guangdong.Using the STR linkage analysis method to investigate the molecular pathogenic mechanism,it was found that 32 cases were deletion⁃type PWS,7 cases of maternal haploid diploid type PWS,14 cases were deletion⁃type AS,and 1 case of paternal haploid diploid type AS.Sequence analysis did not detect the mutant AS of UBE3A gene.Chromosome microarray analysis further clarified the location of chromosome breaks,and additionally detected 6 cases of chromosomal microdeletion/microduplication syndrome with phenotype overlap with PWS/AS.Conclusion In this study,a genetic analysis program for PWS and AS was established to significantly reduce the age of diagnosis of PWS and AS patients,and to determine the types of molecular defects,as well as early intervention to help improve the prognosis of children.

关 键 词：Prader⁃Willi综合征 ANGELMAN综合征 分子诊断 

分 类 号：R725.9[医药卫生—儿科] R440[医药卫生—临床医学]