Unstable Robertsonian translocations der(13;15)(q10;q10): Heritable chromosome fission without phenotypic effect in two kindreds

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...

Full description

Saved in:
Bibliographic Details
Published in:American journal of medical genetics. Part A 2005-07, Vol.136A (1), p.25-30
Main Authors: Perry, Jo, White, Sue M., Nouri, Sara, Bain, Sharon M., Hutchinson, Rhonda G., La, Phung, Northrop, Emma, Eyre, Helen J., Pertile, Mark D., Hocking, Trudy A., Thompson, Elizabeth M., Yu, Sui, Choo, K.H. Andy, Slater, Howard R.
Format: Article
Language:English
Subjects:
Autoantigens - immunology
Centromere Protein A
Chromosomal Proteins, Non-Histone - immunology
Chromosome Banding
chromosome fission
Chromosomes, Human, Pair 13 - genetics
Chromosomes, Human, Pair 15 - genetics
dicentric
Family Health
Female
Fluorescent Antibody Technique - methods
Humans
In Situ Hybridization, Fluorescence
Karyotyping
Male
Pedigree
Robertsonian translocation
Translocation, Genetic
unstable
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. © 2005 Wiley‐Liss, Inc.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.30763