Genome-wide detection of uniparental disomy in a fetus with intrauterine growth restriction using genotyping microarrays.

OBJECTIVE To present the clinical and molecular features of a fetus with confined trisomy 16 mosaicism with maternal uniparental disomy (UPD), using various prenatal diagnostic techniques. MATERIALS AND METHODS Chromosomal karyotyping was performed on samples of chorionic villi, amniotic fluid cells, amniotic membrane, umbilical cord, fetal skin, and placenta from a fetus with elevated nuchal translucency. Polymorphic short tandem repeat markers and Affymetrix single nucleotide polymorphism (SNP) mapping chips were used for molecular analyses. RESULTS Karyotypes from chorionic villi and amniocytes showed 47,XX,+16 and 46,XX, respectively. Short tandem repeat markers on chromosome 16 suggested maternal UPD for chromosome 16. Affymetrix 10K SNP mapping chips were used to simultaneously confirm the difference in karyotypes between the placenta and amniocytes and to diagnose UPD for chromosome 16. Fetal ultrasonography and magnetic resonance imaging identified severe intrauterine growth restriction (IUGR). Autopsy revealed IUGR, incomplete lobulation of bilateral lungs, and malrotation of the intestines. The karyotypes of umbilical cord, fetal skin and amniotic membrane were 46,XX, and the trisomy 16 karyotype appeared to be confined to the placenta. CONCLUSION UPD should be investigated as a possible etiology in all cases of unexplained IUGR. SNP microarrays can be useful for confirming this diagnosis.