The First Neocentric, Discontinuous, and Complex Small Supernumerary Marker Chromosome Composed of 7 Euchromatic Blocks Derived from 5 Different Chromosomes

Background: The majority of small supernumerary marker chromosomes (sSMCs) are derived from one single chromosome. Complex sSMCs instead consist of two to three genomic segments, originating from different chromosomes. Additionally, discontinuous sSMCs have been seen; however, all of them are derived from one single chromosome. Here, we reported a 41 year-old patient with infertility, hypothyroidism, rheumatism, and degenerative spine and schizoaffective disorder, being a carrier of a unique, complex, and discontinuous sSMC. Methods: The sSMC was characterized in detail by banding and molecular cytogenetics including fluorescence in situ hybridization (FISH) and array-comparative genomic hybridization (aCGH), as well as by optical genome mapping (OGM). Results: The neocentric sSMC characterized here contained seven portions of five different chromosomes and was present in similar to 50% of both peripheral blood cells and buccal mucosa cells. aCGH and OGM revealed gains of 8q12.3q12.3, 8q22.3-8q23.1, 9q33.3-9q34.11, 14q21.1-14q21.1, 14q21.1-14q21.2, 15q21.2-15q21.2, and 21q21.1-21q21.1. Furthermore, glass-needle based microdissection and reverse FISH, as well as FISH with locus-specific probes confirmed these results. The exact order of the involved euchromatic blocks could be decoded by OGM. Conclusions: Among the >7000 reported sSMCs in the literature, this is the only such complex, discontinuous, and neocentric marker with a centric minute shape.

Automated summary

This study reported a unique, complex, and discontinuous small supernumerary marker chromosome (sSMC) in a patient with multiple diseases.