Trisomy 20p resulting from inverted duplication and neocentromere formation

Normal human centromeres contain large tandem arrays of alpha-satellite DNA of varying composition and complexity. However, a new class of mitotically stable marker chromosomes which contain neocentromeres formed from genomic regions previously devoid of centromere activity was described recently. T hese neocentromeres are fully functional yet lack the repeat sequences trad itionally associated with normal centromere function. We report here a supe rnumerary marker chromosome derived from the short arm of chromosome 20 in a patient with manifestations of dup(20p) syndrome. Detailed cytogenetic, F ISH, and polymorphic microsatellite analyses indicate the de novo formation of the marker chromosome during meiosis or early postzygotically, involvin g an initial chromosome breakage at 20p11.2, followed by an inverted duplic ation of the distal 20p segment due to rejoining of sister chromatids and t he activation of a neocentromere within 20p12. This inv dup(20p) marker chr omosome lacks detectable centromeric a-satellite and pericentric satellite III sequences, or centromere protein CENP-B. Functional activity of the neo centromere is evidenced by its association with 5 different, functionally c ritical centromere proteins: CENP-A, CENP-C, CENP-E, CENP-F, and INCENP. Fo rmation of a neocentromere on human chromosome 20 has not been reported pre viously and in this context represents a new mechanism for the origin of du p(20p) syndrome. (C) 1999 Wiley-Liss, Inc.