罕见母源性单亲异二体引起的Prader-Willi综合征1例  

A rare case of Prader-Willi syndrome caused by maternal uniparental heterodisomy

作　　者：周建勋 吴轲 周红梅 Zhou Jianxun;Wu Ke;Zhou Hongmei(Neonatology Department,Quzhou Maternity and Child Health Care Hospital,Quzhou 324000,China;Laboratory of Prenatal Diganosis Center,Quzhou Maternity and Child Health Care Hospital,Quzhou 324000,China;Prenatal Diganosis Center,Quzhou Maternity and Child Health Care Hospital,Quzhou 324000,China)

机构地区：[1]衢州市妇幼保健院新生儿科,衢州324000 [2]衢州市妇幼保健院产前诊断实验室,衢州324000 [3]衢州市妇幼保健院产前诊断中心,衢州324000

出　　处：《国际遗传学杂志》2024年第5期366-371,共6页International Journal of Genetics

基　　金：2023年衢州市级指导性科技攻关项目(2023ZD084)。

摘　　要：目的分析1例Prader-Willi综合征在产前诊断中无法检出的原因。方法患儿,女,1天,疑似Prader-Willi综合征。胎儿期无创产前筛查提示15号染色体异常,产前诊断结果为常规染色体核型分析和染色体微阵列分析正常。应用全外显子组测序技术(whole exome sequencing,WES)对该新生儿进行检测。后续用甲基化特异性多重连接依赖性探针扩增技术(methylation-specific multiplex ligation-dependent probe amplification,MS-MLPA)验证全外显子组测序结果。结果家系全外显子组测序检测提示患儿的两条15号染色体均来自母亲。MLPA结果提示父源性甲基化异常,两项技术证实了该患儿为15号染色体母源性单亲异二体造成的Prader-Willi综合征。结论当产前无创筛查检出15号染色体非整倍体,应在补充报告中提示胎儿存在单亲异二体(uniparental heterodisomy,UPhD)和单亲同二体(uniparental isodisomy,UPiD)的可能性,建议采用家系WES或MS-MLPA排除UPD相关疾病。Objective To analyze the cause of a prenatal missed diagnosis of Prader-Willi syndrome.Methods The proband was a 1-day-old female with suspected Prader-Willi syndrome.Non-invasive prenatal screening suggested an abnormality of chromosome 15,and the results of conventional karyotype analysis and chromosomal microarray analysis in prenatal diagnosis were normal.Whole exome sequencing(WES)was used to detect the newborn.Methylation-specific multiplex ligation-dependent probe amplification(MS-MLPA)was used to verify the result of WES.Results Trio-WES showed maternal UPD of the entire chromosome 15.The MLPA result suggested paternal methylation abnormalities.Both genetic tests confirmed that the newborn was Prader-Willi syndrome caused by maternal uniparental heterodisomy of chromosome 15.Conclusion When the result of non-invasive prenatal screening shows chromosome 15 aneuploidy,the possibility of uniparental heterodisomy and uniparental homodisomy should be suggested in the supplementary report.Trio-WES or MS-MLPA is recommended to exclude UPD-related diseases.

关 键 词：PRADER-WILLI综合征 单亲二倍体 无创产前筛查 

分 类 号：R722.1[医药卫生—儿科]