Mosaic deletion-duplication syndrome of chromosome 3: prenatal molecular cytogenetic diagnosis using cultured and uncultured amniocytes and association with fetoplacental discrepancy.

OBJECTIVE: To present prenatal molecular cytogenetic diagnosis of mosaicism for terminal 3p deletion and distal 3q duplication using cultured and uncultured amniocytes, and the association with fetoplacental discrepancy.

MATERIALS, METHODS, AND RESULTS: A 35-year-old primigravid woman was referred for genetic counseling at 21 weeks of gestation because of 20% (5/25 colonies) mosaicism for add(3)(p26) detected by amniocentesis. Repeated amniocenteses were performed. Array comparative genomic hybridization (aCGH) and interphase fluorescence in situ hybridization (FISH) were applied in the uncultured amniocytes. aCGH analysis detected 0.15-Mb microdeletion of 3p26.3 with CHL1 haploinsufficiency and a 49.42-Mb duplication of 3q24-q29 in the uncultured amniocytes. Interphase FISH analysis revealed 27.3% mosaicism (12/44 cells) in the uncultured amniocytes. Metaphase FISH analysis revealed 23.3% mosaicism (7/30 cells) in the cultured amniocytes. Conventional cytogenetic analysis showed a karyotype of 46,XX,der(3)(qter → q24::p26.3 → qter)[10]/46,XX[20] (33% mosaicism). Subsequent fetal blood sampling showed a karyotype of 46,XX,der(3) (qter→q24::p26.3→qter)[5]/46,XX[35] (12.5% mosaicism). The parents elected to terminate the pregnancy, and a malformed fetus was delivered at 24 weeks of gestation with characteristic facial dysmorphism and clinodactyly of the hands. Cytogenetic analysis of the extraembryonic tissues revealed the results of 46,XX (40 cells) in placenta, 25% mosaicism (10/40 cells) in amniotic membrane and 50% mosaicism (20/40 cells) in umbilical cord.

CONCLUSION: Our presentation highlights the utility of molecular cytogenetic technologies in prenatal diagnosis of rare mosaic chromosome rearrangements and provides evidence for fetoplacental discrepancy under such circumstances.