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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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Array-CGH chromosome 16 profile. A) Genomic imbalances on patient BV chromosome 16, with magnification of the deleted region and B) the contained genes.
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Figure 4: Array-CGH chromosome 16 profile. A) Genomic imbalances on patient BV chromosome 16, with magnification of the deleted region and B) the contained genes.

Mentions: Array-CGH analyses revealed a chromosome 20 normal profile in all patients (Figure 3). Surprisingly, BV was found to be carrier of a 1.9 Mb deletion between 67228076 and 69164712 nucleotides (hg18 NCBI build36) on chromosome 16q22.1 (Figure 4a and 4b). The 1.9 Mb deleted region identified in BV contains 42 genes (Figure 4b), 27 of which with a known function, making it hard to link deletion for the genes with the patient's phenotype. Since the proband's mother had died, assessment of the de novo origin of the anomaly could not be established.


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)

Array-CGH chromosome 16 profile. A) Genomic imbalances on patient BV chromosome 16, with magnification of the deleted region and B) the contained genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Array-CGH chromosome 16 profile. A) Genomic imbalances on patient BV chromosome 16, with magnification of the deleted region and B) the contained genes.
Mentions: Array-CGH analyses revealed a chromosome 20 normal profile in all patients (Figure 3). Surprisingly, BV was found to be carrier of a 1.9 Mb deletion between 67228076 and 69164712 nucleotides (hg18 NCBI build36) on chromosome 16q22.1 (Figure 4a and 4b). The 1.9 Mb deleted region identified in BV contains 42 genes (Figure 4b), 27 of which with a known function, making it hard to link deletion for the genes with the patient's phenotype. Since the proband's mother had died, assessment of the de novo origin of the anomaly could not be established.

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