Hum Genet (1986) 72: 25-26 © Springer-Verlag 1986 A possible new type of chromosome rearrangement: telomere-centromere translocation (tct) followed by double duplication A. Aurias and B. Dutrillaux Structure et Mutagen~se Chromosomiques, CNRS UA N. 620, Institut Curie, Section de Biologie, 26 Rue d'Ulm, F-75231 Paris, Cddex 05, France Summary. The reassessment of a case of complex inter- chromosomal rearrangement after breakage at centromeric and telomeric regions, and the comparison with four other in- dependently published cases suggested the existence of a new type of rearrangement. It would consist of: formation of an isochromosome after breakage at a centromeric region, dupli- cation of the telomeric region of another chromosome, and reassociation of the nonduplicated arm of the first chromo- some with the duplicated telomeric region of the second chro- mosome. The reassessment of a complex chromosomal rearrangement between chromosomes 1 and 4, with an isochromosome for the short arm of chromosome 4 (Andr6 et al. 1976), and the review of published isochromosomes for autosomal arms lead us to propose the existence of a new type of anomaly. It would consist of: 1. The breakage in the centromeric region of one chromo- some and in the telomeric region of another chromosome. 2. The duplication of one arm of the chromosome broken in its centromeric region, leading to the formation of an iso- chromosome. 3. The duplication of a segment near to the broken telomeric region of the other chromosome. 4. A translocation of the non-duplicated arm of the first chro- mosome onto the end of the duplicated telomeric region of the second chromosome (Fig. 1). In the case previously published by one of us, as a trisomy 4p, by formation of an isochromosome (Andr6 et al. 1976), there was a translocation of the long arm of chromosome 4 onto the end of the short arm of chromosome 1. A new analy- sis of the results using various chromosome banding tech- niques, and especially R and T-banding (RHG, THA, RBA, ISCN 1978) indicated that there is an enlargement of the distal region of the short arm of chromosome 1 (Fig. 2). This en- largement seems to result from the duplication of the T-band existing on this chromosome arm. This duplication could either be direct, or more probably inverted. Following the publication of this first case, a series of other cases of isochromosomes for the short arms of chromosome 9 (Herva and Koivisto 1979; Sandig et al. 1979; Smith et al. Offprint requests to: A. Aurias, CNRS UA N. 620, Institut Curie, Sec- tion de Biologie, 26 Rue d'Ulm, F-75231 Paris, C6dex 05, France 1978) and of chromosome 5 (Leschot and Lim 1979) were in- dependently published. In these four cases the mechanism seems to be similar, since an isochromosome for a short arm was formed after breakage at the centromeric region, or at the very proximal region of the long arm; and the long arm was translocated onto the end of another chromosome: 18p, 15p, 7q, and 2q in the four observations cited above, respectively. Unfortunatly, no T-banding and no high resolution band- ing were used, and it is very difficult to check the possibility that the breakages in the telomeric regions were associated with a duplication of these regions from the published pic- tures. However, in the case of i(5p), in which the long arm of chromosome 5 was translocated onto the terminal region of the long arm of chromosome 2, there is clearly a very large R- band, or negative G-band (Fig.3 in Leschot and Lim 1979), which may correspond to a duplication of 2q37. It has been proposed that both in constitutional (Lejeune et al. 1972) and in induced rearrangements (Muleris et al. 1984; Paravatou-Petsota et al. 1985; Dutrillaux et al. 1981) centromeric and telomeric regions are more frequently in- volved than expected. Thus, rearrangements between these two regions must often occur. However, if they lead to a dupli- cation, especially of a whole chromosome arm, a strong selec- tion bias should exist for the ascertainment of this rearrange- ment in human pathology. Only the rearrangements duplicat- ing chromosome arms which trisomy is compatible with life can be expected, as is the case for chromosomes 4, 5, and 9. As we shall see in another report (Aurias et al. 1986), this type of rearrangement may also occur in somatic cells. It can be postulated also that this rearrangement may take place within one and the same chromosome. Then, we should ex- pect the formation of an isochromosome for one arm, and the loss of the other arm, which would be an acentric ring. In- deed, this could explain how isochromosomes arise. Fig. 1. Schematic representation of the rearrangement