A novel test for NIPD of DMD/BMD by relative haplotype dosage

Here, the suthors describe the development of an accurate and affordable test for the non-invasive prenatal diagnosis (NIPD) of Duchenne and Becker muscular dystrophies (DMD/BMD). Cell-free DNA (cfDNA) was extracted from maternal blood and prepared for massively parallel sequencing (MPS) on an Illumina MiSeq by targeted capture enrichment of SNPs across the dystrophin gene on chromosome X. Sequencing data was analysed by relative haplotype dosage (RHDO). Seven healthy pregnant donors and two pregnant DMD carriers all bearing a male fetus were recruited through the NIPSIGEN study. NIPD testing was conducted by RHDO analysis for X-linked disorders where the genomic DNA from the CVS (for healthy pregnant donors) or from the proband (for pregnant DMD carriers) was used to identify the reference haplotype. Results for all patients showed a test accuracy of 100%, when the calculated fetal fraction was > 4%, and correlated with known outcomes. A recombination event was also detected in a DMD patient. This new test for NIPD of DMD/BMD was shown to be accurate and reliable during initial stages of validation. It is also feasible for implementation into clinical service.

Parks M, Court S, Cleary S, et al. Non-invasive prenatal diagnosis of Duchenne and Becker muscular dystrophies by relative haplotype dosage. Prenat Diagn. 2016 Jan 29. [Epub ahead of print]