Prenatal diagnosis of trisomy 3 mosaicism.

OBJECTIVES: To present the clinical, cytogenetic, and molecular cytogenetic findings of prenatally diagnosed trisomy 3 mosaicism. CASE AND METHODS: Trisomy 3 mosaicism is rare, and only two cases of prenatally diagnosed trisomy 3 mosaicism have been reported. Amniocentesis, performed for AMA, revealed a karyotype of 47,XX, + 3[8]/46,XX[27]. Periumbilical blood sampling (PUBS) showed 46,XX in 100 cells. Fluorescence in situ hybridization (FISH) analysis using an alpha satellite chromosome 3 probe confirmed the cytogenetic findings. A repeat amniocentesis confirmed mosaicism for trisomy 3 (47,XX, + 3[1]/46,XX[18]). The infant was delivered by elective C-section because of the presence of IUGR and oligohydramnios. The baby had normal physical findings at birth except for symmetric IUGR, apparently resulting from the placental trisomic cell lines. At delivery, chromosome analysis of 50 cells each from blood, placenta, and umbilical cord revealed 46,XX in all cells. FISH analysis of amniotic fluid cells (54 nuclei), peripheral blood (50 nuclei), umbilical cord fibroblasts (57 nuclei), and placental tissue (52 nuclei) demonstrated two signals in 200 nuclei (i.e., 46,XX) and three signals in 13 nuclei (i.e., 47,XX, + 3). At 11 months of age, the baby was progressing normally. CONCLUSION: A diagnosis of trisomy 3 mosaicism is problematic for patients and clinicians. This is only the third case of trisomy 3 mosaicism identified at amniocentesis. Ultrasound, PUBS, and evaluation of placental tissues and postnatal peripheral blood, were useful in providing information regarding the fetal involvement of trisomy 3. Additional cases of prenatally diagnosed mosaicism for rare trisomies are necessary to more accurately assess the significance of these findings.

Prenatal diagnosis of a rare inherited heterochromatic variant chromosome 4.

Heterochromatic chromosome polymorphisms have been extensively reported. Most are associated with C-band positive regions located on chromosomes 1, 9, 16, and Y. We report a prenatal case of a rare heterochromatic variant on chromosome 4. Amniocentesis was performed on a 35-year-old white female for AMA. The karyotype was 46,XY,add(4)(q35)?. One chromosome 4 homolog had an additional dark band at the terminus of the long arm. Parental chromosome analyses revealed that the chromosome 4 was maternally inherited. The mother and fetus were both Q and C-band positive and NOR and DAPI Distamycin staining negative. FISH using Y, 4, and 9 whole chromosome paint (WCP), centromere probes for all chromosomes (Cytocell, Chromoprobe Multiprobe-I System, Rainbow Scientific, Inc., Windsor, CT), alpha-satellite probes for 13/21, 14/22 (D13Z1/D21Z1; D14Z1/D22Z1, Oncor, Gaithersburg, MD), and the 15 PWS/Angelman probe (LSI SNRPN, D15Z1, PML, Vysis, Inc., Downers Grove, IL) were negative. The TelVysion 4q telomere probe (D4S2930, Vysis, Inc.) was positive. A phenotypically normal male was born at 37 weeks. Follow up studies on placenta, cord, cord blood, and foreskin confirmed the prenatal results. Based on these findings, it appears that this chromosome 4 was a rare heterochromatic variant. Heterochromatic variants have been demonstrated to have no phenotypic effect on carriers. This case illustrates the importance of reporting unusual variant chromosomes for genetic counseling purposes. To the best of our knowledge, this is the first report of a heterochromatic variant involving part of the long arm of chromosome 4 in a phenotypically normal mother and child.