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

Abstract

AbstractSmall supernumerary marker chromosomes (sSMCs) are additional derivative chromosomes present in an otherwise numerically and structurally normal karyotype. They may derive from each of the 24 human chromosomes, and most contain a normal centromeric region with an alphoid sequence from a single chromosome. The majority of human chromosomes have a unique centromeric DNA-sequence enabling their indubitable characterization. However, chromosomes 14 and 22 share a common centromeric sequence D14/22Z1, and sSMCs with this DNA-stretch can derive from either chromosome. Euchromatin-carrying sSMCs(14 or 22) may be further characterized by molecular cytogenetics. However, in most diagnostic laboratories, heterochromatic sSMCs cannot be differentiated between chromosomes 14 or 22 derivation and are often reported as der(14 or 22). Still, heterochromatic sSMC(14 or 22) can be distinguished from each other using the D22Z4 probe (non-commercial) localized to 22p11.2. Herein, 355 sSMC(14 or 22) analyzed in the authors’ laboratory during the last ~ 20 years are summarized to address the questions: (1) What are the true frequencies of chromosome 14- and chromosome 22- derived sSMCs within D14/22Z1-positive cases? (2) Does sub-characterization of sSMC(14) and sSMC(22) make a difference in routine diagnostics? These questions could be answered as follows: (ad 1) within the studied group of sSMCs ~ 40% are derived from chromosome 14 and ~ 60% from chromosome 22; (ad 2) the knowledge on exact sSMC origin can help to save costs in routine diagnostics; i.e. in a clinically abnormal person with sSMC(14) a test for uniparental disomy is indicated, which is not necessary if a chromosome 22 origin for the sSMC was determined.