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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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FISH analysis with chromosome 20-specific α-satellite DNA probes. FISH results on r(20), indicating alphoid-specific heteromorphism suitable to discriminate between the two homologous chromosomes 20 (arrowed) in DG, CD, PE and FMA patients. In FL, BV and BD no polymorphic signals on chromosome 20 homologous have been identified. See text for explanation
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Figure 1: FISH analysis with chromosome 20-specific α-satellite DNA probes. FISH results on r(20), indicating alphoid-specific heteromorphism suitable to discriminate between the two homologous chromosomes 20 (arrowed) in DG, CD, PE and FMA patients. In FL, BV and BD no polymorphic signals on chromosome 20 homologous have been identified. See text for explanation

Mentions: FISH investigations with a chromosome 20-specific α-satellite DNA probes showed the derivation of the ring chromosomes from chromosome 20 (Figure 1). The analysis of at least 100 interphase nuclei and 60 lymphocyte metaphases of each patient indicated that no more than 1% of cells were monosomic for chromosome 20 due to the loss of r(20) chromosome because of its mitotic instability. The presence of variant in size alphoid tandem repeats monitored by FISH signals of different intensities (low/high) was also observed on chromosome 20 centromeres (Figure 1). An alphoid-specific heteromorphism suitable to discriminate between the two homologous chromosomes 20 was detected in DG, CD, PE and FMA patients, whereas in FL and BV the signals were similar in size on both chromosome 20 centromeres (Figure 1). Careful scoring of about 15 metaphases from the informative patients allowed us to distinguish the apparently normal chromosome 20 from the r(20) chromosome using the "identity" of the structure of the centromeric constriction. Indeed the "low" intensity signal discriminating r(20) chromosome from its "high" signal normal homologous was present in the not "circularized" chromosome 20 in the cell line with normal karyotype of DG, CD and FMA likewise the "high" intensity signal of r(20) chromosome of PE (Figure 1).


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)

FISH analysis with chromosome 20-specific α-satellite DNA probes. FISH results on r(20), indicating alphoid-specific heteromorphism suitable to discriminate between the two homologous chromosomes 20 (arrowed) in DG, CD, PE and FMA patients. In FL, BV and BD no polymorphic signals on chromosome 20 homologous have been identified. See text for explanation
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: FISH analysis with chromosome 20-specific α-satellite DNA probes. FISH results on r(20), indicating alphoid-specific heteromorphism suitable to discriminate between the two homologous chromosomes 20 (arrowed) in DG, CD, PE and FMA patients. In FL, BV and BD no polymorphic signals on chromosome 20 homologous have been identified. See text for explanation
Mentions: FISH investigations with a chromosome 20-specific α-satellite DNA probes showed the derivation of the ring chromosomes from chromosome 20 (Figure 1). The analysis of at least 100 interphase nuclei and 60 lymphocyte metaphases of each patient indicated that no more than 1% of cells were monosomic for chromosome 20 due to the loss of r(20) chromosome because of its mitotic instability. The presence of variant in size alphoid tandem repeats monitored by FISH signals of different intensities (low/high) was also observed on chromosome 20 centromeres (Figure 1). An alphoid-specific heteromorphism suitable to discriminate between the two homologous chromosomes 20 was detected in DG, CD, PE and FMA patients, whereas in FL and BV the signals were similar in size on both chromosome 20 centromeres (Figure 1). Careful scoring of about 15 metaphases from the informative patients allowed us to distinguish the apparently normal chromosome 20 from the r(20) chromosome using the "identity" of the structure of the centromeric constriction. Indeed the "low" intensity signal discriminating r(20) chromosome from its "high" signal normal homologous was present in the not "circularized" chromosome 20 in the cell line with normal karyotype of DG, CD and FMA likewise the "high" intensity signal of r(20) chromosome of PE (Figure 1).

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