Abstract:

A pregnant woman with left renal cyst and excessive amniotic fluid diagnosed by prenatal ultrasound was reported. After consultation, genetic testing of the fetus was requested to clarify the clinical diagnosis. Subsequently, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) were used to analyze the DNA of fetal amniotic fluid cells. CMA results showed that there was a chimeric uniparental disomy (UPD) with a fragment size of about 18.6 Mb in the 11p15.5p15.1 region of the fetal chromosome. Simultaneously, no clear pathogenic gene mutations were found within the WES detection range. To clarify the parental origin of fetal chimeric UPD, the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) for Beckwith-Wiedemann syndrome (BWS) was further used to detect abnormal methylation in the fetal imprinted region. The MS-MLPA results demonstrated that the methylation level in the imprinting center region 1 (ICR1) region of the fetus increased, while the methylation level in the ICR2 region decreased. Therefore, it can be determined that the fetal 11p15.5p15.1 region is a paternal chimeric UPD, thereby confirming that the fetus is BWS. Prenatal ultrasound of BWS is often a non-specific manifestation, which easily leads to missed diagnosis and misdiagnosis. Therefore, it is extremely important to carry out correct and targeted molecular diagnostic techniques to avoid the birth of defective children.

Key words: Beckwith-Wiedemann syndrome, Uniparental disomy, Chromosomes, Microarray analysis, Methylation, Prenatal diagnosis