Chromosomal mosaicism in prenatal diagnosis: a problem still unsolved

Area of Science:

• Genetics
• Prenatal Diagnostics

Background:

• Distinguishing true chromosomal mosaicism from pseudomosaicism is critical for accurate prenatal diagnosis.
• Amniocentesis and chorionic villus sampling (CVS) can yield results that are difficult to interpret due to mosaicism.

Purpose of the Study:

• To illustrate the challenges in differentiating chromosomal mosaicism from pseudomosaicism using case studies.
• To highlight the variability in aberrant cell line detection across different fetal tissues and culture conditions.

Main Methods:

• Case study analysis of six patients undergoing prenatal genetic testing.
• Comparison of cytogenetic findings from amniotic fluid cells, fetal blood, and cultivated fibroblasts.
• Evaluation of results from chorionic villus sampling (CVS).

Main Results:

• True mosaicism cases (45,X/46,XX and 46,XY/47,XXY) showed reduced aberrant cell line expression in amniotic fluid compared to fetal blood and fibroblasts.
• Pseudomosaicism cases (trisomy 2 and 10) likely resulted from pre-existing or in vitro mutations.
• A case of true chromosome 20 mosaicism suggested tissue-specific mosaicism.
• A 45,X/46,XY CVS case demonstrated abnormal cell line detection limited to extraembryonic tissue.

Conclusions:

• Interpreting mosaicism in prenatal diagnostics requires careful consideration of cell type and tissue origin.
• Variability in aberrant cell line detection underscores the complexity of diagnosing chromosomal mosaicism.
• Further research is needed to refine diagnostic criteria for mosaicism detected via amniocentesis and CVS.