1. ¹INSERM U491; Université de la Méditerranée; Faculté de Médecine de la Timone, Marseille, France
2. ²Laboratorio di Citogenetica, Istituto G Gaslini, Universita di Genova, Genova, Italy
3. ³Department of Medical Genetics, The Children's Memorial Health Institute, Warszawa, Poland
4. ⁴Département de Génétique, Hôpital d'enfants de la Timone, Marseille, France
5. ⁵Service de Génétique Médicale, Hôpital Font-Pré, Toulon, France
6. ⁶Centre de Génétique Chromosomique, Hôpital St Vincent de Paul, Lille, France
7. ⁷Génétique, Frelinghien, France
8. ⁸Institute of Human Genetics, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany

Correspondence: Dr Marie-Genevieve Mattei, Inserm U491, Universite de la mediterranee, Faculté de Médecine, 27 Boulevard Jean Moulin, Marseille F-13385, France. Tel: +33 (0)4 91 25 71 73; Fax: +33 (0)4 91 80 43 19; E-mail: genevieve.mattei@medecine.univ-mrs.fr

Received 18 July 2006; Revised 21 November 2006; Accepted 6 December 2006; Published online 31 January 2007.

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.