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Genetic investigations on 8 patients affected by ring 20 chromosome syndrome.

Giardino D, Vignoli A, Ballarati L, Recalcati MP, Russo S, Camporeale N, Marchi M, Finelli P, Accorsi P, Giordano L, La Briola F, Chiesa V, Canevini MP, Larizza L - BMC Med. Genet. (2010)

Bottom Line: FISH and array-CGH experiments indicate that cryptic deletions on chromosome 20 are not the cause of the r(20) chromosome associated disease.Moreover, no evidence of chromosome 20 uniparental disomy was found.Behavioural problems also seem to be associated with higher percentages of r(20) chromosome cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratorio di Citogenetica Medica e Genetica Molecolare, IRCCS Istituto Auxologico Italiano Milan, Italy. giardino@auxologico.it

ABSTRACT

Background: Mosaic Chromosome 20 ring [r(20)] is a chromosomal disorder associated with a rare syndrome characterized by a typical seizure phenotype, a particular electroclinical pattern, cognitive impairment, behavioural problems and absence of a consistent pattern of dysmorphology. The pathogenic mechanism underlying seizures disorders in r(20) syndrome is still unknown. We performed a detailed clinical and genetic study on 8 patients with r(20) chromosome, aimed at detecting the genetic mechanism underlying r(20) syndrome.

Methods: We submitted 8 subjects with a previous diagnosis of ring 20 chromosome mosaicism to a clinical re-evaluation, followed by cytogenetic, FISH, array-CGH and molecular analyses. The genetic study was also extended to their available parents.

Results: FISH and array-CGH experiments indicate that cryptic deletions on chromosome 20 are not the cause of the r(20) chromosome associated disease. Moreover, no evidence of chromosome 20 uniparental disomy was found. Analysis of FISH signals given by variant in size alphoid tandem repeats probes on the normal chromosome 20 and the r(20) chromosome in the mosaic carriers suggests that the r(20) chromosome is the same chromosome not circularized in the "normal" cell line.

Conclusions: Higher percentages of r(20) chromosome cells were observed to be related with precocious age at seizure onset and with resistance to antiepileptic drug treatment. Behavioural problems also seem to be associated with higher percentages of r(20) chromosome cells. Our results suggest that an epigenetic mechanism perturbing the expression of genes close to the telomeric regions, rather than deletion of genes located at the distal 20p and/or 20q regions, may underlie the manifestation of r(20) syndrome.

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Results of segregation analysis from parents to probands of chromosome 20 microsatellites.
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Figure 5: Results of segregation analysis from parents to probands of chromosome 20 microsatellites.

Mentions: Occurrence of either whole or segmental chromosome 20 uniparental disomy (UPD) was investigated by segregation analysis of polymorphic loci from parents to proband. In all cases the informative markers evidenced a biparental contribution. In BV family microsatellite analysis only allowed exclusion of paternal UPD, because the mother was deceased. Segregation analysis from FL grandmother to FL through FMA indicated the biparental contribution of chromosome 20 and the absence of recombination along the chromosome, which appears to be transmitted in an identical form across two generations (Figure 5).


Genetic investigations on 8 patients affected by ring 20 chromosome syndrome.

Giardino D, Vignoli A, Ballarati L, Recalcati MP, Russo S, Camporeale N, Marchi M, Finelli P, Accorsi P, Giordano L, La Briola F, Chiesa V, Canevini MP, Larizza L - BMC Med. Genet. (2010)

Results of segregation analysis from parents to probands of chromosome 20 microsatellites.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2967536&req=5

Figure 5: Results of segregation analysis from parents to probands of chromosome 20 microsatellites.
Mentions: Occurrence of either whole or segmental chromosome 20 uniparental disomy (UPD) was investigated by segregation analysis of polymorphic loci from parents to proband. In all cases the informative markers evidenced a biparental contribution. In BV family microsatellite analysis only allowed exclusion of paternal UPD, because the mother was deceased. Segregation analysis from FL grandmother to FL through FMA indicated the biparental contribution of chromosome 20 and the absence of recombination along the chromosome, which appears to be transmitted in an identical form across two generations (Figure 5).

Bottom Line: FISH and array-CGH experiments indicate that cryptic deletions on chromosome 20 are not the cause of the r(20) chromosome associated disease.Moreover, no evidence of chromosome 20 uniparental disomy was found.Behavioural problems also seem to be associated with higher percentages of r(20) chromosome cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratorio di Citogenetica Medica e Genetica Molecolare, IRCCS Istituto Auxologico Italiano Milan, Italy. giardino@auxologico.it

ABSTRACT

Background: Mosaic Chromosome 20 ring [r(20)] is a chromosomal disorder associated with a rare syndrome characterized by a typical seizure phenotype, a particular electroclinical pattern, cognitive impairment, behavioural problems and absence of a consistent pattern of dysmorphology. The pathogenic mechanism underlying seizures disorders in r(20) syndrome is still unknown. We performed a detailed clinical and genetic study on 8 patients with r(20) chromosome, aimed at detecting the genetic mechanism underlying r(20) syndrome.

Methods: We submitted 8 subjects with a previous diagnosis of ring 20 chromosome mosaicism to a clinical re-evaluation, followed by cytogenetic, FISH, array-CGH and molecular analyses. The genetic study was also extended to their available parents.

Results: FISH and array-CGH experiments indicate that cryptic deletions on chromosome 20 are not the cause of the r(20) chromosome associated disease. Moreover, no evidence of chromosome 20 uniparental disomy was found. Analysis of FISH signals given by variant in size alphoid tandem repeats probes on the normal chromosome 20 and the r(20) chromosome in the mosaic carriers suggests that the r(20) chromosome is the same chromosome not circularized in the "normal" cell line.

Conclusions: Higher percentages of r(20) chromosome cells were observed to be related with precocious age at seizure onset and with resistance to antiepileptic drug treatment. Behavioural problems also seem to be associated with higher percentages of r(20) chromosome cells. Our results suggest that an epigenetic mechanism perturbing the expression of genes close to the telomeric regions, rather than deletion of genes located at the distal 20p and/or 20q regions, may underlie the manifestation of r(20) syndrome.

Show MeSH
Related in: MedlinePlus