title: Prenatal molecular cytogenetic diagnosis of partial tetrasomy 10p due to neocentromere formation in an inversion duplication analphoid marker chromosome.
abstract: Neocentromeres are fully functional centromeres found on rearranged or marker chromosomes that have separated from endogenous centromeres. Neocentromeres often result in partial tri- or tetrasomy because their formation confers mitotic stability to acentric chromosome fragments that would normally be lost. We describe the prenatal identification and characterization of a de novo supernumerary marker chromosome (SMC) containing a neocentromere in a 20-wk fetus by the combined use of comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). GTG-banding of fetal metaphases revealed a 47,XY,+mar karyotype in 100% of cultured amniocytes; parental karyotypes were both normal. Although sequential tricolor FISH using chromosome-specific painting probes identified a chromosome 10 origin of the marker, a complete panel of chromosome-specific centromeric satellite DNA probes failed to hybridize to any portion of the marker. The presence of a neocentromere on the marker chromosome was confirmed by the absence of hybridization of an all-human-centromere alpha-satellite DNA probe, which hybridizes to all normal centromeres, and the presence of centromere protein (CENP)-C, which is associated specifically with active kinetochores. Based on CGH analysis and FISH with a chromosome 10p subtelomeric probe, the marker was found to be an inversion duplication of the distal portion of chromosome 10p. Thus, the proband's karyotype was 47,XY,+inv dup(10)(pter-->p14 approximately 15::p14 approximately 15-->neo-->pter), which is the first report of partial tetrasomy 10p resulting from an analphoid marker chromosome with a neocentromere. This study illustrates the use of several molecular strategies in distinguishing centric alphoid markers from neocentric analphoid markers.
authors.affiliation: Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA. brynn.levy@mssm.edu
authors.forename: B
authors.initials: B
authors.lastname: Levy
authors.forename: P
authors.initials: P
authors.lastname: Papenhausen
authors.forename: J
authors.initials: J
authors.lastname: Tepperberg
authors.forename: T
authors.initials: T
authors.lastname: Dunn
authors.forename: S
authors.initials: S
authors.lastname: Fallet
authors.forename: M
authors.initials: M
authors.lastname: Magid
authors.forename: N
authors.initials: N
authors.lastname: Kardon
authors.forename: K
authors.initials: K
authors.lastname: Hirschhorn
authors.forename: P
authors.initials: P
authors.lastname: Warburton
mesh_terms: D000328:Adult; D000649:Amniocentesis; D000782:Aneuploidy; D002503:Centromere / Q000235:genetics*; D002869:Chromosome Aberrations / Q000175:diagnosis* / Q000235:genetics; D002871:Chromosome Banding; D025063:Chromosome Disorders; D007446:Chromosome Inversion; D020223:Chromosome Painting; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D015342:DNA Probes / Q000235:genetics; D004276:DNA, Satellite / Q000235:genetics; D005260:Female; D020440:Gene Duplication; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D008423:Maternal Age; D011247:Pregnancy; D018566:Pregnancy, High-Risk; D011296:Prenatal Diagnosis
chemical_list: D015342:DNA Probes; D004276:DNA, Satellite; D005819:Genetic Markers