Live birth after PGD with confirmation by a comprehensive approach (karyomapping) for simultaneous detection of monogenic and chromosomal disorders.
Preimplantation genetic diagnosis (PGD) for monogenic disorders has the drawback of time and cost associated with tailoring a specific test for each couple, disorder, or both. The inability of any single assay to detect the monogenic disorder in question and simultaneously the chromosomal complement of the embryo also limits its application as separate tests may need to be carried out on the amplified material. The first clinical use of a novel approach ('karyomapping') was designed to circumvent this problem. In this example, karyomapping was used to confirm the results of an existing PGD case detecting both chromosomal abnormalities and a monogenic disorder (Smith-Lemli-Opitz [SLO] syndrome) simultaneously. The family underwent IVF, ICSI and PGD, and both polar body and cleavage stage biopsy were carried out. Following whole genome amplification, array comparative genomic hybridisation of the polar bodies and minisequencing and STR analysis of single blastomeres were used to diagnose maternal aneuploidies and SLO status, respectively. This was confirmed, by karyomapping. Unlike standard PGD, karyomapping required no a-priori test development. A singleton pregnancy and live birth, unaffected with SLO syndrome and with no chromosome abnormality, ensued. Karyomapping is potentially capable of detecting a wide spectrum of monogenic and chromosome disorders and, in this context, can be considered a comprehensive approach to PGD.
['Natesan|Senthilkumar A|SA|', 'Handyside|Alan H|AH|', 'Thornhill|Alan R|AR|', 'Ottolini|Christian S|CS|', 'Sage|Karen|K|', 'Summers|Michael C|MC|', 'Konstantinidis|Michalis|M|', 'Wells|Dagan|D|', 'Griffin|Darren K|DK|']
D001757:Blastomeres D002869:Chromosome Aberrations D025063:Chromosome Disorders D002875:Chromosomes D055028:Comparative Genomic Hybridization D004252:DNA Mutational Analysis D005260:Female D005307:Fertilization in Vitro D006801:Humans D007231:Infant, Newborn D007621:Karyotyping D050498:Live Birth D008297:Male D059705:Polar Bodies D011247:Pregnancy D011256:Pregnancy Outcome D019836:Preimplantation Diagnosis D019082:Smith-Lemli-Opitz Syndrome D020554:Sperm Injections, Intracytoplasmic
PGD Karyomapping polar body aneuploidy Smith Lemli Opitz syndrome embryo biopsy