title: Recurrent rearrangements in the proximal 15q11-q14 region: a new breakpoint cluster specific to unbalanced translocations.
abstract: Unbalanced translocations, that involve the proximal chromosome 15 long arm and the telomeric region of a partner chromosome, result in a karyotype of 45 chromosomes with monosomy of the proximal 15q imprinted region. Here, we present our analysis of eight such unbalanced translocations that, depending on the parental origin of the rearranged chromosome, were associated with either Prader-Willi or Angelman syndrome. First, using FISH with specific BAC clones, we characterized the chromosome 15 breakpoint of each translocation and demonstrate that four of them are clustered in a small 460 kb interval located in the proximal 15q14 band. Second, analyzing the sequence of this region, we demonstrate the proximity of a low-copy repeat 15 (LCR15)-duplicon element that is known to facilitate recombination events at meiosis and to promote rearrangements. The presence, in this region, of both a cluster of translocation breakpoints and a LCR15-duplicon element defines a new breakpoint cluster (BP6), which, to our knowledge, is the most distal breakpoint cluster described in proximal 15q. Third, we demonstrate that the breakpoints for other rearrangements including large inv dup (15) chromosomes do not map to BP6, suggesting that it is specific to translocations. Finally, the translocation breakpoints located within BP6 result in very large proximal 15q deletions providing new informative genotype-phenotype correlations.
authors.affiliation: INSERM U491, Université de la Méditerranée, Faculté de Médecine de la Timone, Marseille, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Mignon-Ravix
authors.forename: Danielle
authors.initials: D
authors.lastname: Depetris
authors.forename: Judith J
authors.initials: JJ
authors.lastname: Luciani
authors.forename: Cristina
authors.initials: C
authors.lastname: Cuoco
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
authors.forename: Chantal
authors.initials: C
authors.lastname: Missirian
authors.forename: Patrick
authors.initials: P
authors.lastname: Collignon
authors.forename: Bruno
authors.initials: B
authors.lastname: Delobel
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Croquette
authors.forename: Anne
authors.initials: A
authors.lastname: Moncla
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kroisel
authors.forename: Marie-Geneviève
authors.initials: MG
authors.lastname: Mattei
mesh_terms: D000328:Adult; D017204:Angelman Syndrome / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D011218:Prader-Willi Syndrome / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D016615:Telomere / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*