Inherited Tetrasomy of the 15p-15q11.2 Region Associated with Normal Phenotypes

We analyzed the 15p-15q11.2 region of human chromosome 15 that was tetrasomic in a three-generation family with a chromosome 15-derived small supernumerary marker chromosome (der15, sSMC). This stable, inherited sSMC was present in four family members. The breakpoint that led to the formation of der15 was established by fluorescence in situ hybridization (FISH) using 18 bacterial artificial chromosomes (BACs) mapping to the pericentric region of 15q. The breakpoint was mapped to an 11 kb sequence in the 15q11.2b sub-band, and it resides in a NF1 pseudogene, within the BAC 810K23 clones. FISH mapping verified the localization of the overlapping 18 BAC clones in the 15q11.2 region, and confirmed that large duplications were spanning to 15q13.1 including the PWS/AS critical region. Carriers of the der15 pseudodicentric isochromosome are healthy, and these cases support that inherited tetrasomy of the 19.4 Mb chromosomal segment of the 15p-q11.2b region has no phenotypic consequences.