title: Unstable Robertsonian translocations der(13;15)(q10;q10): heritable chromosome fission without phenotypic effect in two kindreds.
abstract: Robertsonian translocations (RTs) are amongst the most common chromosome abnormalities, but being essentially balanced are not usually associated with phenotypic abnormality. Despite being dicentric, RTs are almost always transmitted stably through cell division without chromosome breakage. We have investigated spontaneous fission of der(13;15)(q10;q10) chromosomes in eight individuals from two unrelated kindreds with a view to assessing clinical significance and to seek an explanation for the peculiar heritable instability displayed by these chromosomes. In Family 1, fission products were observed in five members in three generations. The instability was observed in cells derived from chorionic villus and lymphocytes. In Family 2, the same phenomenon was observed in amniocytes from two separate pregnancies and maternal blood lymphocytes. Detailed FISH analysis of these RTs showed them to be dicentric with an unremarkable pericentromeric structure. Notably, combined immunofluoresence and FISH analysis showed the presence of the centromere-specific proteins CENP-A and CENP-E, consistent with functional dicentricity in >75% of cells analyzed. The fission products are, therefore, presumed to be the result of sporadic, bipolar kinetochore attachment, anaphase bridging with resultant inter-centromeric breakage in a small proportion of mitoses. None of the eight carriers shows phenotypic abnormality and therefore, for prenatal counseling purposes, there appears to be no increased specific risk associated with this phenomenon.
authors.affiliation: Murdoch Childrens Research Institute, Genetic Health Services Victoria, Victoria, Australia.
authors.forename: Jo
authors.initials: J
authors.lastname: Perry
authors.forename: Sue M
authors.initials: SM
authors.lastname: White
authors.forename: Sara
authors.initials: S
authors.lastname: Nouri
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Bain
authors.forename: Rhonda G
authors.initials: RG
authors.lastname: Hutchinson
authors.forename: Phung
authors.initials: P
authors.lastname: La
authors.forename: Emma
authors.initials: E
authors.lastname: Northrop
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Eyre
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pertile
authors.forename: Trudy A
authors.initials: TA
authors.lastname: Hocking
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Thompson
authors.forename: Sui
authors.initials: S
authors.lastname: Yu
authors.forename: K H Andy
authors.initials: KH
authors.lastname: Choo
authors.forename: Howard R
authors.initials: HR
authors.lastname: Slater
mesh_terms: D001324:Autoantigens / Q000276:immunology; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology; D002871:Chromosome Banding; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005192:Family Health; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D010375:Pedigree; D014178:Translocation, Genetic
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; C068688:centromere protein E