Can a blood test miss mosaicism?

[Anonymous]

Can a blood test miss mosaicism?

[Genetic Counselor]

Yes. A blood-based genetic test can sometimes fail to detect mosaicism, particularly when the genetically altered cell population is absent or present at a very low percentage in the blood.

This happens because mosaicism does not necessarily affect every tissue equally.

Remember that the body develops from a fertilised egg through repeated cell divisions. If a genetic change occurs during embryonic development, the affected cells may contribute to certain tissues but not others.

For example, a person may have a chromosomal abnormality in some skin cells but not in the blood cells. In such a situation, a routine blood chromosome analysis may produce a normal result even though mosaicism is present elsewhere in the body.

This is why the choice of tissue is important in genetic testing.

Different sample types may be considered depending on the suspected condition:
– Peripheral blood: Commonly used for chromosome analysis, microarray testing and molecular genetic investigations.
– Buccal swab: Collects cells from the inside of the cheek and may help identify mosaicism not detected in blood.
– Skin biopsy: Can provide fibroblast cells for chromosome or molecular analysis, particularly when tissue-specific mosaicism is suspected.
– Urine epithelial cells: May be useful for investigating certain forms of mosaicism, depending on the suspected genetic condition.
– Affected tissue: In some situations, testing tissue directly involved in the clinical presentation may provide more useful information.
The appropriate sample depends on the suspected genetic alteration and the laboratory technique being used.

Different testing methods also have different abilities to detect mosaicism.

For example:
– Karyotyping: Can identify chromosomal abnormalities in individual cells, but detection depends on the number of cells examined.
– Chromosomal microarray (CMA): Can detect certain chromosomal imbalances and mosaic changes, although sensitivity depends on the platform, tissue and percentage of affected cells.
– FISH: Can examine individual cells for specific chromosomal abnormalities and may help identify low-level mosaicism.
– Next-generation sequencing (NGS): Can identify low-level mosaic variants when the sequencing depth, variant characteristics and bioinformatics pipeline are suitable.
If clinical findings strongly suggest mosaicism despite a normal blood result, a geneticist or genetic counsellor may recommend testing an additional tissue.

However, a cheek swab or skin biopsy is not automatically required for everyone. The decision should be based on the clinical presentation and suspected genetic condition.

The key message: A normal genetic test result from blood does not always completely exclude mosaicism. Sometimes, the genetic alteration may be present in another tissue that was not tested.

[Author]

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