To present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from ring chromosome, or r(4) by spectral karyotyping (SKY), fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (aCGH).
Materials, Methods, and Results
A 37-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a de novo ring-shaped sSMC in 16 of 31 amniocyte colonies. The parental karyotypes were normal. Level II ultrasound findings were unremarkable. Repeated amniocentesis revealed a karyotype of 47,XX,+mar/46,XX. The sSMC was characterized by SKY and FISH, which showed a chromosome 4 origin of the sSMC. aCGH demonstrated a 21.7-Mb gain in the gene dosage encompassing the region of 4p12→q13.2. The sSMC was r(4)(p12q13.2). The fetal karyotype was 47,XX,+r(4)(p12q13.2)/46,XX. The pregnancy was subsequently terminated. The fetus postnatally manifested hypertelorism, epicanthic folds, a prominent nose, a triangular face, low-set ears, clinodactyly of the fingers, and small big toes. Postnatal cytogenetic analyses of fetal and extraembryonic tissues revealed the karyotypes of 47,XX,+r(4)/46,XX in cord blood, 47,XX,+r(4)/48,XX,+r(4),+r(4)/46,XX in umbilical cord, 47,XX,+r(4)/47,XX,+dic r(4)/46,XX in skin, 47,XX,+r(4)/46,XX in amnion, and 47,XX,+r(4)/47,XX,+dic r(4)/46,XX in placenta.
SKY, FISH, and aCGH are helpful in genetic counseling of prenatally detected sSMCs by providing the immediate and thorough information on the origin and genetic component of the sSMC.