If mosaicism is suspected and a blood test is negative, what strategy increases the likelihood of detecting a variant?

• A. Conclude no mutation exists.
• B. Test additional tissues or use deeper sequencing.
• C. Repeat blood test only.
• D. Perform karyotyping.

Answer: (B)

Mosaicism means the variant is present only in a subset of cells, so a negative blood test doesn’t rule out a mutation elsewhere in the body. To increase the chance of finding it, you’d look in other tissues where the mutated cells might be more represented (for example, skin, buccal cells, or cultured cells) or you’d use deeper sequencing on the available tissue. Testing additional tissues broadens the sampling to different cell populations, raising the probability that at least one sample contains the variant. Deeper sequencing raises sensitivity by increasing the number of reads, making it possible to detect low-level mosaic variants that a standard depth might miss.

Repeating the same blood test without increasing depth doesn’t overcome the issue of tissue distribution. Karyotyping looks for large chromosomal changes and typically misses small sequence variants or low-level mosaicism, so it’s not the best strategy when a mosaic single-nucleotide variant is being considered.