engleski

Parental origin of the stable dicentric X chromosome

Dicentrics are chromosomes with two centromeres. This structurally aberrant chromosomes are highly unstable, and rare constant member of the human karyotype. On the other hand, stable dicentrics usually present one active and one inactivate centromere and behave like monocentrics. The investigation conducted so far disclosed several types and different mechanisms of origin of dicentric chromosomes. In this report we present the results of cytogenetic and molecular study in a 5-years old girl with mild dismorphism, growth retardation, behavioral problems and structural rearrangement of X chromosome. Cytogenetic analysis was performed on short-term lymphocyte cultures of the proband and her parents. Chromosomes were GTG and CBG banded, while X chromosome inactivation was studied using RBG method. Fluorescence in situ hybridisation (FISH) was carried out on patients metaphase chromosomes and interphase cells with X chromosome painting and centromeric probes. The parental origin of aberrant chromosome was investigated by DNA polymorphisms analysis. Barr body analysis was performed on buccal mucosa smears stained by routine acetic orcein. Both parents presented normal karyotype. Leukocyte chromosome analyisis of the proband revealed one normal and one aberrant X chromosome. The rearranged X is a large submetacentric with one primary constriction and two blocks of C-staining. FISH analysis revealed that aberrant chromosome is composed entirely of the X chromosome material. Interphase FISH with alpha satellite X centromere probe revealed two mosaic cell lines. Three signals were observed in 84.5%, and one signal in 15.5% of interphase cells. Replication analysis showed that the normal X always early replicates, while the dicentric was late replicating in all investigated cells. The buccal smear revealed X-chromosome positive cells, and in some cells the Barr body was bipartite. Molecular analysis of DNA polymorphisms indicates that the dicentric is of paternal origin. Based on this study the karyotype of the patients is 45, X/46, X, psu idic(X)(q22.3), with the trisomy Xpter-q22.3 and monosomy Xqter-q22.3. We suggest that dicentric X is the result of isolocal break in the two chromatides of the paternal X chromosome, subsequent rejoining of broken ends, followed by inactivation of one centromere.

dicentric chromosomes; FISH; DNA polymorphism

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