Prenatal diagnosis of mosaic tetrasomy 18p.

OBJECTIVE: To present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome derived from isochromosome 18p, by interphase fluorescence in situ hybridization (FISH) on uncultured amniocytes.

CASE REPORT: A 41-year-old woman underwent amniocentesis at 18 weeks of gestation, because of advanced maternal age. Amniocentesis revealed a de novo supernumerary isochromosome 18p in two of 14 colonies of cultured amniocytes. Repeated amniocentesis was performed at 22 weeks of gestation. Interphase FISH analysis on uncultured amniocytes showed four 18p11.32-specific probe (RP11-324G2) signals in 5.7% (3/53 cells) of uncultured amniocytes. A multiplex ligation-dependent probe amplification P095 test kit and array comparative genomic hybridization analysis did not detect genomic imbalance in chromosome 18. Cytogenetic analysis of cultured amniocytes at repeated amniocentesis revealed a karyotype of 47,XY,+i(18)(p10)[3]/46,XY[23]. The pregnancy was carried to 38 weeks of gestation, and a healthy 3120 g male baby was delivered. When examined at 2 months of age, the infant was normal in growth and development, without phenotypic abnormalities. The cord blood had a karyotype of 46,XY. Polymorphic DNA marker analysis excluded uniparental disomy 18. Interphase FISH analysis on uncultured urinary cells showed 9.4% (3/32 cells) mosaicism for tetrasomy 18p.

CONCLUSION: There is cytogenetic discrepancy between amniocytes and cord blood lymphocytes in prenatally detected mosaic tetrasomy 18p. Interphase FISH on uncultured amniocytes has the advantage of rapid confirmation of low-level mosaicism for tetrasomy 18p at amniocentesis.