Telomere shortening and telomere position effect in mild ring 17 syndrome

Epigenetics & Chromatin

Adriano Angioni¹  Antonella Sgura³  Francesca Romana Lepri¹  Serena Russo¹  Laura Ciocca¹  Elisa Pisaneschi¹  May El Hachem⁵  Stefano Petrocchi¹  Simona Grotta¹  Raffaella Cusmai⁴  Maria Cristina Digilio⁶  Pietro Sirleto¹  Gemma D’Elia¹  Letizia Da Sacco²  Maria Cristina Roberti¹  Andrea Masotti²  Francesco Berardinelli³  Cecilia Surace¹ 

[1] Cytogenetics and Molecular Genetics Unit, ‘Bambino Gesù’ Children’s Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy;Gene Expression-Microarrays Laboratory, ‘Bambino Gesù’ Children’s Hospital, IRCCS, Rome, Italy;Department of Biology, University ‘Roma Tre’, Rome, Italy;Neurology Unit, ‘Bambino Gesù’ Children’s Hospital, IRCCS, Rome, Italy;Dermatology Unit, ‘Bambino Gesù’ Children’s Hospital, IRCCS, Rome, Italy;Medical Genetics Unit, ‘Bambino Gesù’ Children’s Hospital, IRCCS, Rome, Italy

关键词: Telomere shortening;    Ring 17 chromosome;    Telomere position effect;    Genetic syndrome;   

Others  :  804917
DOI  :  10.1186/1756-8935-7-1

 received in 2013-09-23, accepted in 2013-12-13,  发布年份 2014

【 摘 要 】

Background

Ring chromosome 17 syndrome is a rare disease that arises from the breakage and reunion of the short and long arms of chromosome 17. Usually this abnormality results in deletion of genetic material, which explains the clinical features of the syndrome. Moreover, similar phenotypic features have been observed in cases with complete or partial loss of the telomeric repeats and conservation of the euchromatic regions. We studied two different cases of ring 17 syndrome, firstly, to clarify, by analyzing gene expression analysis using real-time qPCR, the role of the telomere absence in relationship with the clinical symptoms, and secondly, to look for a new model of the mechanism of ring chromosome transmission in a rare case of familial mosaicism, through cytomolecular and quantitative fluorescence in-situ hybridization (Q-FISH) investigations.

Results

The results for the first case showed that the expression levels of genes selected, which were located close to the p and q ends of chromosome 17, were significantly downregulated in comparison with controls. Moreover, for the second case, we demonstrated that the telomeres were conserved, but were significantly shorter than those of age-matched controls; data from segregation analysis showed that the ring chromosome was transmitted only to the affected subjects of the family.

Conclusions

Subtelomeric gene regulation is responsible for the phenotypic aspects of ring 17 syndrome; telomere shortening influences the phenotypic spectrum of this disease and strongly contributes to the familial transmission of the mosaic ring. Together, these results provide new insights into the genotype-phenotype relationships in mild ring 17 syndrome.

【 授权许可】

   
2014 Surace et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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