Identification of a jumping translocation following pre‐implantation genetic diagnosis

Abstract

Jumping translocations (JTs) were first described in a patient with Prader–Willi syndrome by Lejeune et al. [1979] and can be defined as non-reciprocal unstable chromosome rearrangements, in which the same donor chromosome segment is translocated to different recipient chromosomes. When occurring as constitutional abnormalities JTs are rare events and are usually ascertained because of clinical abnormalities. They have been associated with recognizable phenotypes such as Down syndrome, Di-George syndrome and Dandy–Walker malformation and have also been found in spontaneous abortions [Levy et al., 2000]. Constitutional JTs often involve an acrocentric chromosome with 15q12 and 22q11.2 breakpoints observed most commonly [Jewett et al., 1998]. Interstitial telomeric sequences have been found in most cases of constitutional JTs and it has been observed that in many JTs at least one of the breakpoints occurs in areas containing repetitive DNA such as telomeric, centromeric, or nucleolar organizing regions, suggesting that regions of homologous repetitive DNA sequences may play an important role in their formation [Vermeesch et al., 1997]. This report describes the unusual transmission of a JT derived from a paternal translocation involving chromosomes 4 and 22, where the donor chromosome 22 with breakpoint 22q11.2 jumped to a different autosome; chromosome 12 in the offspring. The JT was ascertained prenatally in one fetus of a twin pregnancy following pre-implantation genetic diagnosis (PGD). To our knowledge this is the first JT detected following PGD involving paternal transmission and adds to the small number of JT cases reported in the literature involving unstable familial translocations. This was the eighth IVF cycle following 7 years of infertility in a couple with polycystic ovaries in the female and azoospermia in the partner. PGD was not performed on the first four IVF cycles undertaken at another clinic, of which three cycles had resulted inmiscarriage in the first trimester. Following the fourth IVF cycle, parental karyotypeswereperformedand themale partner revealed a karyotype with 45,XY,der(4)t(4;22)(q35;q11.2),-22 involving a derivative chromosome 4 resulting from a translocation between chromosomes 4 and 22. There is loss of the reciprocal 22 translocation product, however cytogenetically there appears to be no apparent loss of euchromatic material. The female partner revealed a 46,XX karyotype.