Familial 18 centromere variant resulting in difficulties in interpreting prenatal interphase FISH

Area of Science:

• Genetics
• Prenatal Diagnosis
• Molecular Cytogenetics

Background:

• Familial centromeric heteromorphism of chromosome 18 can complicate prenatal diagnosis.
• Interphase fluorescence in situ hybridization (FISH) is a key technique for prenatal genetic analysis.
• Accurate interpretation of FISH results is crucial for diagnosing fetal abnormalities.

Observation:

• A case of maternal chromosome 18 centromeric heteromorphism was transmitted to the fetus.
• Prenatal interphase FISH initially suggested a 22q11.2 microdeletion due to signal loss.
• Analysis of maternal buccal cells confirmed the heteromorphism and aided in reinterpreting FISH results.

Findings:

• The study identified a familial centromeric heteromorphism of chromosome 18.
• Misinterpretation of prenatal interphase FISH occurred due to the heteromorphism, mimicking a 22q11.2 microdeletion.
• Locus-specific (LSI) probes proved more effective than centromeric probes for interphase analysis in this case.

Implications:

• Accurate prenatal diagnosis requires careful interpretation of FISH results, especially in cases with chromosomal variations.
• Locus-specific probes are superior to centromeric probes for interphase FISH analysis.
• Development of high-quality LSI probes for chromosomes 18, X, and Y could prevent misdiagnosis and reduce unnecessary investigations.