“先天生长过剩综合征”又称“Beckwith-Wiedemann syndrome（BWS）”，是对胎儿及婴幼儿生存发育危害重大的遗传疾病，且致多种恶性肿瘤的高发。前期，申请者证实了家族性BWS发病中存在临床及分子遗传学的子代“早现”现象，并发现其（表观）遗传异常表现模式，而BWS遗传早现的机制仍不清楚。申请者提出母源NCBI37:11:g.2023019T>C阻碍OCT4与ICR1结合，促进DNMTs表达，引起ICR1-GOM，抑制CTCF，使IGF2表达增强而H19沉默，且DNA高甲基化率在逐代传递中累积，引起早现。本项目将结合靶突变BWS动物模型证实上述假说。同时，应用以高级三维成像系列新技术为主的超声平台对各子代不同发育时期的BWS进行诊断，制定规范化BWS超声诊断评分系统，并获得超声影像特征与BWS遗传早现的对应关系，为实现超声医学对BWS遗传早现的早期诊断及随访提供重要依据。

"Congenital overgrowth syndrome", also known as "Beckwith-Wiedemann syndrome (BWS)" is a type of genetic disease that is harmful to the survival and development of the fetus and infants, also causing a high incidence of a variety of malignant tumors, the pathogenesis is not fully elucidated. The applicant's previous study confirmed the presence of “anticipation” at clinical phenotypes and molecular genetics aspects for familial BWS, and reported the epigenetic patterns and characteristics of BWS anticipation. However, there is still no research on the mechanism of familiar BWS anticipation. The applicant proposed that maternal NCBI37: 11: g. 2023019T > C blocks OCT4 binding to ICR1, promotes DNMTs expression, causes ICR1-GOM, inhibits CTCF, enhances IGF2 expression and silences H19, and DNA hypermethylation ratio is transmitted from generation to generation, finally causing anticipation of BWS. This project plans to confirm the above hypothesis in combination with the target mutant humanized BWS animal model. At the same time, the ultrasound platform based on series of the advanced real-time three-dimensional new imaging technology is applied to diagnose the BWS for different developmental stages in the offspring, and the standardized BWS ultrasonic diagnosis scoring system will be established. Furthermore, the relationships between the ultrasound imaging features and the BWS genetic anticipation degree will be explored. These will provide an important theoretical basis for the early diagnosis and follow-up of BWS genetic anticipation by ultrasonic medicine.