title: Common structural features characterize interstitial intrachromosomal Xp and 18q triplications.
abstract: Rare intrachromosomal triplications producing partial tetrasomies have been reported for a number of chromosomes. A detailed molecular characterization, necessary to define the mechanism of their formation, has so far been lacking. We report on the detailed clinical, cytogenetic, and molecular characterization of two triplications, one de novo involving chromosome 18q, the other familial on chromosome Xp. The clinical phenotype of the patient with 18q triplication, very likely due to overexpression of one or more of the genes in the region, consists mainly of facial dysmorphisms and developmental delay. The familial Xp triplication does not cause an increase in the number of copies of any gene and is almost certainly a polymorphism. The rearrangements are actually complex duplications/triplications. In both patients, their proximal breakpoints are located within complex segmental duplications, one containing the VCX gene cluster on chromosome Xp, the other the TCEB3 genes on chromosome 18q. A proximal duplicated region is also present in both patients. All junctions we analyzed were formed by non-homologous end joining (NHEJ). The structural features shared between our patients suggest the involvement of a common mechanism in the genesis of interstitial intrachromosomal triplications.
authors.affiliation: Istituto Scientifico E. Medea, Bosisio Parini (LC), Italy. roberto.giorda@bp.lnf.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Giorda
authors.forename: Silvana
authors.initials: S
authors.lastname: Beri
authors.forename: M Clara
authors.initials: MC
authors.lastname: Bonaglia
authors.forename: Luigina
authors.initials: L
authors.lastname: Spaccini
authors.forename: Barbara
authors.initials: B
authors.lastname: Scelsa
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Manolakos
authors.forename: Erika
authors.initials: E
authors.lastname: Della Mina
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccone
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D056905:Chromosome Breakpoints; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics*; D003001:Cloning, Molecular; D059766:DNA End-Joining Repair; D002658:Developmental Disabilities / Q000235:genetics* / Q000473:pathology; D000075065:Elongin; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000473:pathology; D018740:Genetic Heterogeneity; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008677:Metaphase; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics; D014314:Trisomy / Q000235:genetics*
chemical_list: C000616397:ELOA protein, human; D000075065:Elongin; D009687:Nuclear Proteins; D014157:Transcription Factors; C404411:VCX protein, human