title: Telomere shortening and telomere position effect in mild ring 17 syndrome.
abstract: 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.
authors.affiliation: Cytogenetics and Molecular Genetics Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Surace
authors.affiliation: Department of Biology, University 'Roma Tre', Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Berardinelli
authors.affiliation: Gene Expression-Microarrays Laboratory, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Masotti
authors.affiliation: Cytogenetics and Molecular Genetics Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Roberti
authors.affiliation: Gene Expression-Microarrays Laboratory, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Da Sacco
authors.affiliation: Cytogenetics and Molecular Genetics Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Gemma
authors.initials: G
authors.lastname: D'Elia
authors.affiliation: Cytogenetics and Molecular Genetics Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Sirleto
authors.affiliation: Medical Genetics Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Digilio
authors.affiliation: Neurology Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cusmai
authors.affiliation: Cytogenetics and Molecular Genetics Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Grotta
authors.affiliation: Cytogenetics and Molecular Genetics Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Petrocchi
authors.affiliation: Dermatology Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Rome, Italy.
authors.forename: May El
authors.initials: ME
authors.lastname: Hachem
authors.affiliation: Cytogenetics and Molecular Genetics Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pisaneschi
authors.affiliation: Cytogenetics and Molecular Genetics Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ciocca
authors.affiliation: Cytogenetics and Molecular Genetics Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Russo
authors.affiliation: Cytogenetics and Molecular Genetics Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Lepri
authors.affiliation: Department of Biology, University 'Roma Tre', Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Sgura
authors.affiliation: Cytogenetics and Molecular Genetics Unit, 'Bambino Gesù' Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Angioni