The aim of this work was to explore the genetic cause of the proband (Ⅲ2) presenting with polyhydramnios and gastroschisis. Copy number variation sequencing (CNV-seq), methylation-specific multiplex PCR (MS-PCR), and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were used to characterize the genetic etiology. CNV-seq revealed a deletion of 732.26 kb at 14q32.2q32.31 in the proband (Ⅲ2) and its mother (Ⅱ2). MS-PCR showed the maternal allele was missing in the proband, while paternal allele was missing in its mother. MS-MLPA showed deletion of the DLK1, MEG3, MIR380, and RTL1 genes of both the proband and its mother. MEG3 imprinting gene methylation increased in the proband, while decreased in its mother. It was indicated that a maternally transmitted deletion was responsible for Kagami–Ogata syndrome in the proband (Ⅲ2), and the de novo paternal deletion resulted in Temple syndrome in the mother (Ⅱ2). Prenatal diagnosis was provided at 17+3 weeks of pregnancy on the mother’s fourth pregnancy (Ⅲ4). Fortunately, the karyotype and single-nucleotide polymorphism array (SNP array) results were normal. The current investigation provided the detection methods for imprinted gene diseases, expanded the phenotype spectrum of the disease, and obtained the insight into the diagnosis, prenatal diagnosis, and genetic counseling of the disease.

Background Cell-free fetal DNA in the maternal plasma is widely used to identify the aneuploid, including trisomy 21, 18, 13 and sex chromosomes. While for the detection of rare autosomal trisomies, the outcome has not come to a consensus. Here we reported a case of trisomy 8 mosaicism (T8M) which was identified by cffDNA screening. Methods Noninvasive prenatal screening (NIPS), fetal karyotyping, single nucleotide polymorphism array (SNP array) and interphase fluorescence in situ hybridization (FISH) analysis were used to characterize etiology in the fetus. Results In this study, trisomy 8 was initially identified by cell-free fetal DNA in the maternal plasma. Ultrasound scans and magnetic resonance imaging observed fetal hydronephrosis and irregular spine. Trisomy 8 mosaicism was diagnosed based on the SNP array and amniocentesis results. The couple decided to continue the pregnancy after genetic counseling and a male infant was delivered. Interphase FISH analysis in the uncultured neonatal cord blood cells confirmed trisomy 8 mosaicism, with a percentage of 10%. In the follow up, periodic fever as well as language retardation was observed, indicating a poor prognosis. Conclusions Our study provided an insight into the identification of low level rare autosomal trisomy mosaicism with cell-free fetal DNA.