Abstract for presentation at 11th International Congress of Human Genetics

Preimplantation genetic diagnosis (PGD) for 45,XY,der(4)t(4;22)(q35;q11.2) with subsequent prenatal karyotype revealing a jumping translocation (JT)

  • Christie Beale, Sydney Genetics Sydney IVF, Australia
  • Mrs Isabel Habibi, Sydney Genetics Sydney IVF, Australia
  • Ms Polihronis Sia, Sydney Genetics, Australia
  • Mr McArthur Steven, Sydney IVF, Australia
  • Dr Livingstone Mark, Sydney IVF, Australia
  • Mr Marshall James, Sydney IVF, Australia
  • Mr Wright Dale, Sydney Genetics Sydney IVF, Australia

    • In vitro fertilisation and PGD for a translocation carrier 45,XY,der(4)t(4;22)(q35;q11.2) resulted in a twin pregnancy after transfer of 2 embryos with normal/balanced result. On ultrasound at 13w0d, one twin had an increased nuchal fold measurement (6.3mm) and congenital heart defect. Amniocentesis was performed at 17w5d. The G-banded karyotype of the structurally abnormal fetus was 47,XY,+21. There was an unexpected 45,XY,der(12)t(12;22)(q24.3;q11.2) karyotype in the other twin. Neither outcome was detectable with the probes used at PGD. Premature labour at 24wks resulted in demise of the abnormal twin with the other showing ongoing healthy development to date.
    FISH studies showed the 4q subtelomere and TUPLE1 locus, but not D22Z1 sequences, on the father’s der(4)t(4;22). FISH mapping with BACs showed the hybridisation of clone 401D16 distal to the 22q11.2 breakpoint. However, it is uncertain if the breakpoint is identical in father and fetus. The UCSC genome browser indicates clone 401D16 lies ~1.0MB distal to the centromere, with 29 known genes and 114 low copy repeat (LCR) sequences. The 22q11.2 region is prone to rearrangements that can be mediated by chromosome 22 LCRs (LCR22)1, which are susceptible to breakage and repair, resulting in translocations, deletions or duplications. JTs are rare constitutional abnormalities and breakpoints are typically found at repeat sequences at telomeric and pericentromeric regions. We propose the der(12) in the fetus may have arisen during gametogenesis following non-homologous recombination between the LCR22-2 region within the father’s der(4)t(4;22) and the telomere at 12q with subsequent stabilising repair of the 4q telomere.

    Reference:
    1. Spiteri et al (2003). Hum.Mol.Genet.12(15):1823-1837.

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