Somatic mosaicism in cases with small supernumerary marker chromosomes

Area of Science:

• Cytogenetics
• Genetics
• Genomic Instability

Background:

• Somatic mosaicism is a common observation in cytogenetics, particularly in cases involving small supernumerary marker chromosomes (sSMC).
• Chromosome instability is a primary driver of large-scale genome variation.
• sSMC cases often exhibit mosaicism, with karyotypes like 47,+mar/46.

Purpose of the Study:

• To investigate the frequency of somatic mosaicism across different patient subgroups with sSMC.
• To analyze the susceptibility of various sSMC types to mosaicism.
• To evaluate the clinical implications and diagnostic limitations of mosaicism in sSMC.

Main Methods:

• Literature review and data collection on patients with sSMC.
• Analysis of reported frequencies of somatic mosaicism in sSMC cohorts.
• Comparison of mosaicism rates between different sSMC subgroups and origins (acrocentric vs. non-acrocentric).

Main Results:

• Out of 3124 sSMC cases reviewed, 1626 (52%) presented with somatic mosaicism.
• Pallister-Killian syndrome cases universally show mosaicism, while Emanuel, cat-eye, and i(18p) syndromes rarely do.
• Non-acrocentric derived sSMCs are less stable and more prone to mosaicism than acrocentric ones.

Conclusions:

• Somatic mosaicism is a significant factor in at least half of all sSMC cases.
• While often clinically silent, mosaicism can alter outcomes, impacting prenatal genetic counseling.
• Array-comparative genomic hybridization (array-CGH) is insufficient for reliably detecting low-level or cryptic mosaicism in sSMC patients.