Prenatal diagnosis of complete maternal uniparental isodisomy of chromosome 4 in a fetus without congenital abnormality or inherited disease-associated variations

BACKGROUND: The prenatal diagnosis of subjects with complete uniparental isodisomy of chromosome 4 (iUPD4) has rarely been reported and poses a great challenge for genetic counseling. In this study, a prenatal case with a high (1 in 58) risk of Down syndrome was diagnosed with iUPD4 by combined chromosomal microarray analysis (CMA), whole exome sequencing (WES) and ultrasound morphology scan. RESULTS: By CMA, a pathogenic copy number variant was not detected; however, a complete maternal iUPD4 was identified in this fetus after analyzing the parental genotype results. To detect potentially autosomal recessive variants, WES was performed. Two missense and two frameshift variants were identified but were predicted with uncertain significance; none of the mutations were definitively associated with congenital abnormality or inherited disease. In addition, a detailed ultrasound morphology scan did not identify any structural abnormalities, facial dysmorphisms or intrauterine growth restriction. The family history was unremarkable. The couple was counseled with the prenatal diagnostic results, and they opted to give birth to the child. No phenotypic abnormalities were observed in this child after the first year of life. CONCLUSION: This study provides further evidence that iUPD4 can result in a healthy live birth and demonstrates that the combined use of CMA, WES and ultrasound technology provides additional information for the prenatal diagnosis and clinical management of rare UPD events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13039-015-0190-z) contains supplementary material, which is available to authorized users.