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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., (Copyright (c) 2004 John Wiley & Sons, Ltd.)

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., (Copyright 2003 Wiley-Liss, Inc.)

Structural chromosome mosaicism is rare. We report a case of prenatal mosaicism for a deletion of chromosome 10(q23). To our knowledge, there are only three reports of prenatally diagnosed cases of del(10)(q23). Two of these cases were due to an inherited fragile site. In the present case amniocentesis revealed 46,XY,del(10)(q23)[9]/46,XY[45]. Follow-up chromosome analysis of peripheral blood and placental tissue from a phenotypically normal liveborn male revealed the del(10)(q23) in only 3/100 blood cells grown in low-folate medium. It appears that prenatally diagnosed deleted (10q) mosaicism represents culture artifact and is not clinically significant., (Copyright 2002 Wiley-Liss, Inc.)

Trisomy 4 mosaicism is rare. To our knowledge only two cases of prenatally diagnosed trisomy 4 mosaicism have been reported. One case resulted in a normal liveborn male, the other resulted in an abnormal liveborn female. The karyotype of our case at the time of amniocentesis was 47,XY,+4[3]/ 46,XY[33] and resulted in a normal liveborn male. FISH analysis using an alpha satellite chromosome 4 probe was performed to confirm the cytogenetic findings. Follow-up chromosome analysis of cord blood, peripheral blood, foreskin, and umbilical cord fibroblasts showed a normal 46,XY male karyotype in all cells. FISH analysis of cord blood, umbilical cord fibroblasts, and amniotic fluid cells demonstrated two signals in 246 nuclei (i.e., 46,XY) and three signals in six nuclei (i.e., 47,XY,+4). Here we describe the present case of trisomy 4 mosaicism, the literature is reviewed, and the significance of this finding is discussed.

Low level chromosome mosaicism found at amniocentesis is problematic for clinicians and patients. We report prenatal diagnosis of a fetus with a rare karyotype of 47,XX, + 15/46,XX. Second trimester amniocentesis was performed for advanced maternal age. Fetal ultrasound revealed a hypoplastic right ventricle and intrauterine growth retardation (IUGR). The rest of the fetal anatomy was within normal limits. A mosaic karyotype of 47,XX, + 15/46,XX was observed. The couple interrupted the pregnancy at 19 weeks by dilation and suction evacuation. Careful evaluation of multiple pieces of fetal parts and placenta revealed one abnormal finding: a single umbilical artery. Cytogenetic metaphase and fluorescent in situ hybridization (FISH) interphase analyses of cells from fetal lung, heart, placenta, and skin revealed the presence of the trisomic line in all tissues. Molecular analysis demonstrated that the origin of the extra chromosome 15 was maternal, the error most likely occurred in meiosis I and the diploid line was of biparental inheritance. This case report discusses the associated findings in this fetus and reviews the literature describing other cases of mosaic trisomy 15.

Two phenotypically abnormal liveborns in whom trisomy 16 mosaicism was diagnosed prenatally by amniocentesis are described. Analysis of a percutaneous umbilical blood sample in one case revealed a normal chromosomal complement. Ultrasound examinations performed at the time of amniocentesis were normal. Serial sonography during the late second and third trimesters demonstrated progressive intrauterine growth retardation (IUGR) in both fetuses and a cardiac defect in one. At birth, both infants had dysmorphic features and multiple congenital anomalies. Trisomy 16 mosaicism was confirmed postnatally in both infants in skin fibroblasts; however, peripheral blood samples contained only chromosomally normal cells. The two mosaic trisomy 16 cases described in this report, together with the five confirmed cases reported previously, demonstrate the need for caution in the counselling of patients when trisomy 16 mosaicism is diagnosed prenatally in amniotic fluid samples. Such cases potentially can result in the birth of dysmorphic infants with significant birth defects, growth retardation, and possible developmental disabilities.

Extra genetic material that is euchromatic is generally regarded to be associated with phenotypic abnormalities. However, recent studies suggest that this is not always the case. Chromosome analysis was performed on amniotic fluid cells from a 37-year-old phenotypically normal patient referred for advanced maternal age. All the cells analysed showed a karyotype of 46,XY,1p+. The 1p+ chromosome had extra genetic material of uncertain origin in chromosome band region 1p21-->31. Chromosome analysis on the father revealed a normal 46,XY male karyotype. The mother's karyotype showed the same 1p+ chromosome. C and Q banding, as well as silver staining studies, in both the mother and the fetus support the interpretation that the extra chromosomal material was euchromatic in nature. This 1p+ chromosome may be characterized as a euchromatic heteromorphism. Euchromatic heteromorphisms not associated with phenotypic abnormalities have been reported for chromosomes 9 and 16. To the best of our knowledge, this is the first report involving this type of cytogenetic anomaly on chromosome number 1 in a phenotypically normal mother and infant.