Clinical, cytogenetic, and molecular analyses of prenatally diagnosed mosaic tetrasomy for distal chromosome 15q and review of the literature

Objectives: To present prenatally detected mosaic tetrasomy for distal chromosome 15q and a review of the literature.

Clinical subject and methods: Amniocentesis was performed at 17 weeks' gestation because of advanced maternal age. Cytogenetic analysis revealed mosaicism for an analphoid supernumerary marker chromosome (SMC). The parental karyotypes were normal. Fluorescence in situ hybridization (FISH) and polymorphic DNA marker analysis were applied to study the origin of the SMC. Level II ultrasound revealed gastric dilation. The pregnancy was terminated, and a malformed fetus was delivered with characteristic dysmorphism. Multiple samplings of fetal and extraembryonic tissues were performed to investigate the mosaicism.

Results: Initial amniocentesis revealed mos 47,XY,+ mar[20]/46,XY[1], and repeat amniocentesis revealed 47,XY,+ mar[28]/46,XY[8]. FISH and polymorphic DNA marker analysis determined an origin from the distal 15q and an inverted duplication of 15q25.3 --> qter for the SMC. Karyotype of the fetus was designated as 47,XY,+ ace i(15) (qter --> q25.3::q25.3 --> qter)/46,XY de novo. The levels of tetrasomy for distal 15q were 28/40 in cord blood, 13/40 in liver, 14/40 in lungs, 27/40 in skin, 0/40 in placenta, and 40/40 in umbilical cord. The placenta showed an equal biparental inheritance (1:1). The umbilical cord inherited one copy of a paternal allele and three copies of a maternal allele (1:3) at distal 15q. Diallelic patterns with dosage ratios (paternal allele: maternal allele) of 1:2.5 in amniocytes, 1:2.3 in amnion, 1:2.2 in cord blood, 1:2.1 in skin, 1:1.4 in liver, and 1:1.4 in lungs. A maternal origin of the mosaic SMC(15) was determined.

Conclusions: A diagnosis of mosaic analphoid SMCs in amniocytes should alert mosaic mirror-image duplication of euchromatin from some distal chromosomal segment such as distal 15q or distal 13q, and a risk for fetal abnormalities. Fetuses with mosaic tetrasomy for distal 15q may be associated with fetoplacental chromosomal discrepancy. Postnatal samplings of umbilical cord, placenta and amniotic membrane may provide additional clues to the cytogenetic discrepancy between fetal and extraembryonic tissues in prenatally detected mosaic analphoid SMCs.