Small supernumerary marker chromosomes derived from chromosome 14 and/or 22

Area of Science:

• Cytogenetics
• Human Genetics
• Molecular Diagnostics

Background:

• Small supernumerary marker chromosomes (sSMCs) are extra chromosomes in individuals with a normal karyotype.
• Chromosomes 14 and 22 share a common centromeric DNA sequence (D14/22Z1), complicating the origin determination of sSMCs.
• Distinguishing between chromosome 14- and 22-derived sSMCs is challenging, especially for heterochromatic variants.

Purpose of the Study:

• To determine the actual frequencies of chromosome 14- and 22-derived sSMCs among D14/22Z1-positive cases.
• To assess the diagnostic utility and cost-saving potential of sub-characterizing sSMC(14) versus sSMC(22) in routine practice.

Main Methods:

• Analysis of 355 D14/22Z1-positive small supernumerary marker chromosomes (sSMCs) over a 20-year period.
• Utilized molecular cytogenetics, including the D22Z4 probe, to differentiate between chromosome 14 and 22 origins.
• Reviewed case data to correlate sSMC origin with diagnostic implications and necessary genetic testing.

Main Results:

• Approximately 40% of the studied sSMCs were derived from chromosome 14, and 60% from chromosome 22.
• Accurate identification of sSMC origin can streamline diagnostic pathways.
• For sSMC(14) in abnormal individuals, testing for uniparental disomy is indicated, unlike for sSMC(22).

Conclusions:

• Chromosome 22 is a more frequent source of D14/22Z1-positive sSMCs than chromosome 14.
• Sub-characterization of sSMC(14) and sSMC(22) offers significant advantages in routine genetic diagnostics.
• Precise sSMC origin determination can prevent unnecessary genetic tests, leading to cost savings and improved diagnostic efficiency.