title: Juxtaposition of heterochromatic and euchromatic regions by chromosomal translocation mediates a heterochromatic long-range position effect associated with a severe neurological phenotype.
abstract: BACKGROUND
  The term "position effect" is used when the expression of a gene is deleteriously affected by an alteration in its chromosomal environment even though the integrity of the protein coding sequences is maintained. We describe a patient affected by epilepsy and severe neurodevelopment delay carrying a balanced translocation t(15;16)(p11.2;q12.1)dn that we assume caused a position effect as a result of the accidental juxtaposition of heterochromatin in the euchromatic region.
  
  
  RESULTS
  FISH mapped the translocation breakpoints (bkps) to 15p11.2 within satellite III and the 16q12.1 euchromatic band within the ITFG1 gene. The expression of the genes located on both sides of the translocation were tested by means of real-time PCR and three, all located on der(16), were found to be variously perturbed: the euchromatic gene NETO2/BTCL2 was silenced, whereas VPS35 and SHCBP1, located within the major heterochromatic block of chromosome 16q11.2, were over-expressed. Pyrosequencing and chromatin immunoprecipitation of NETO2/BTCL2 and VPS35 confirmed the expression findings. Interphase FISH analysis showed that der(16) localised to regions occupied by the beta satellite heterochromatic blocks more frequently than der(15).
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first report of a heterochromatic position effect in humans caused by the juxtaposition of euchromatin/heterochromatin as a result of chromosomal rearrangement. The overall results are fully in keeping with the observations in Drosophila and suggest the occurrence of a human heterochromatin position effect associated with the nuclear repositioning of the der(16) and its causative role in the patient's syndromic phenotype.
authors.affiliation: Laboratory of Medical Cytogenetics and Molecular Genetics, Istituto Auxologico Italiano, Cusano Milanino 20095, Italy. finelli@auxologico.it.
authors.forename: Palma
authors.initials: P
authors.lastname: Finelli
authors.forename: Silvia Maria
authors.initials: SM
authors.lastname: Sirchia
authors.forename: Maura
authors.initials: M
authors.lastname: Masciadri
authors.forename: Milena
authors.initials: M
authors.lastname: Crippa
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Recalcati
authors.forename: Daniela
authors.initials: D
authors.lastname: Rusconi
authors.forename: Daniela
authors.initials: D
authors.lastname: Giardino
authors.forename: Laura
authors.initials: L
authors.lastname: Monti
authors.forename: Francesca
authors.initials: F
authors.lastname: Cogliati
authors.forename: Francesca
authors.initials: F
authors.lastname: Faravelli
authors.forename: Federica
authors.initials: F
authors.lastname: Natacci
authors.forename: Leonardo
authors.initials: L
authors.lastname: Zoccante
authors.forename: Bernardo Dalla
authors.initials: BD
authors.lastname: Bernardina
authors.forename: Silvia
authors.initials: S
authors.lastname: Russo
authors.forename: Lidia
authors.initials: L
authors.lastname: Larizza