Thalassaemia is the commonest monogenic disease and causes a health and economic burden worldwide. Karyomapping can be used for pre-implantation genetic testing of monogenic disorders (PGT-M). This study applied karyomapping in two PGT-M cycles and made a comparison to polymerase chain reaction (PCR). Two families at risk of having beta-thalassaemia-haemoglobin E disease offspring decided to join the project and informed consent was obtained. Karyomapping results of family A (beta-thalassaemia (c.41_42delTCTT)-Hb E (c.26G>A) disease) revealed four normal, two beta-thalassaemia traits, one Hb E trait and six affected. Three embryos exhibited unbalanced chromosomes. One normal male embryo was transferred. Karyomapping results of family B (beta-thalassaemia (c.17A>T)-Hb E (c.26G>A) disease) revealed six Hb E traits and three affected. Three embryos were chromosomally unbalanced. One Hb E trait embryo was transferred. Two successful karyomapping PGT-M were performed, including deletion and single-base mutations. Karyomapping provides accuracy as regards the protocol and copy number variation which is common in pre-implantation embryos. Impact StatementWhat is already known on this subject? Thalassaemia syndrome is the commonest monogenic disease and causes a health and economic burden worldwide. Modern haplotyping using SNP array (aSNP) and karyomapping algorithms can be used for pre-implantation genetic testing of monogenic disorders (PGT-M). However, few clinical karyomapping PGT-M cycles have been done and validated so far.What do the results of this study add? Two successful clinical PGT-M cycles for beta-thalassaemia (c.41_42delTCTT and c.17A>T mutations)-haemoglobin E (c.26G>A) disease were performed using karyomapping. The outcome was two healthy babies. Multiplex fluorescent polymerase chain reaction (PCR) with mini-sequencing was also used for confirmation mutation analysis results. PCR confirmed haplotyping results in all embryos. Six embryos from both PGT-M cycles exhibited unbalanced chromosomes evidenced by aSNP.What are the implications of these findings for clinical practice and/or further research? Karyomapping provides accurate information quickly and the outcomes of the study will save time as regards protocol development, provide a usable universal PGT-M protocol and add additional copy number variation (CNV) information, chromosome number variation being a common issue in pre-implantation embryos.
Keywords: Beta-thalassaemia–haemoglobin E disease; copy number variation (CNV); embryo selection; haplotyping; karyomapping; pre-implantation genetic testing for monogenic disease (PGT-M).