Mosaic variegated aneuploidy without microcephaly: implications for cytogenetic diagnosis

Area of Science:

• Genetics and Molecular Biology
• Clinical Genetics
• Cancer Genetics

Background:

• Mosaic variegated aneuploidy (MVA) is a rare chromosomal disorder characterized by multiple trisomies and a non-specific phenotype.
• MVA is associated with an increased risk of malignancy, underscoring the need for accurate diagnosis.

Observation:

• A patient presented with features suggestive of MVA, initially suspected as trisomy 19 mosaicism.
• Peripheral blood karyotype revealed mosaic trisomies including trisomy 8, 19, 18, and 9.
• Skin fibroblast studies showed a normal 46,XX karyotype, and no BUB1B gene mutations were found.

Findings:

• The case demonstrates a complex chromosomal abnormality with multiple aneuploidies in blood cells.
• The absence of BUB1B mutations in this patient suggests alternative genetic mechanisms in MVA.
• Low-level mosaic aneuploidies can be challenging to interpret and may not always be cell culture artifacts.

Implications:

• This case emphasizes the importance of comprehensive evaluation for MVA, even with low percentages of aneuploidies.
• Early and accurate diagnosis of MVA is crucial for monitoring and managing the associated malignancy risk.
• Further research is needed to elucidate the genetic underpinnings and diagnostic criteria for MVA.