Andrea P. Twomey¹, Paisu Tang¹, Anke E. Kohfahl¹, David Amor², Sharyn E. Stock-Myer¹

¹Virtus Diagnostics, Melbourne IVF, 344 Victoria Parade, Victoria 3002

²Department of Paediatrics, University of Melbourne, Level 2, West Building Royal Children’s Hospital, 50 Flemington Road, Victoria 3052

Exclusion testing allows couples to avoid having an affected child without having to undergo genetic testing themselves for the condition.  Embryos which inherit the haplotype passed on from the affected grandparent are deemed to be ‘at risk’ and therefore not suitable for transfer. We offer exclusion preimplantation genetic diagnosis (PGD) testing using Karyomapping technology to couples at risk of inheriting late onset single gene diseases. This technique utilises approximately 300,000 SNPs spread across the genome in the form of a SNP array which is used to perform linkage analysis as well as detect chromosome imbalances.

We recently provided PGD to a couple seeking exclusion testing for Familial Alzheimers Disease caused by a known pathogenic mutation in the PSEN1 gene that had been previously detected in her affected parent. In their first IVF cycle, from 11 embryos tested none was suitable for transfer, having been diagnosed as at risk of carrying the affected allele or having aneuploidy. During analysis an incidental microdeletion at Xp22.31 was detected in several male embryos and subsequently found in the mother. On further investigation this microdeletion was determined to be a risk factor for autism and we were requested to also test for this in future cycles. In the following IVF cycle Karyomapping was used to analyse for the presence of this Xp22.31 microdeletion as well as for the initial exclusion test for Familial Alzheimers disease.

Exclusion testing using Karyomapping linkage analysis allows us to offer PGD to couples wishing to avoid having a child with a late onset disease without the need for direct mutation detection. However this technology can also reveal incidental findings which may influence future clinical decisions.

Biography

I have more than 20 years experience working as a scientist in human molecular genetic diagnosis. I helped set up molecular genetic diagnostic testing at Monash Medical Centre and have worked in preimplantation genetic diagnosis at Virtus Diagnostics (Melbourne IVF) for the past 8 years.
I am a certified member of the Human Genetics Society of Australasia (Diagnostic Genomics).