Non‐invasive prenatal diagnosis of Duchenne and Becker muscular dystrophies by relative haplotype dosage†. (23rd February 2016) - Parks, Michael
Abstract: Objective: Development of an accurate and affordable test for the non‐invasive prenatal diagnosis of Duchenne and Becker muscular dystrophies (DMD/BMD) to implement in clinical practice. Method: Cell‐free DNA was extracted from maternal blood and prepared for massively parallel sequencing on an Illumina MiSeq by targeted capture enrichment of single nucleotide polymorphisms (SNPs) across the dystrophin gene on chromosome X. Sequencing data were analysed by relative haplotype dosage. Results: Seven healthy pregnant donors and two pregnant DMD carriers all bearing a male fetus were recruited through the non‐invasive prenatal diagnosis for single gene disorders study. Non‐invasive prenatal diagnosis testing was conducted by relative haplotype dosage analysis for X‐linked disorders where the genomic DNA from the chorionic villus sampling (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. Conclusion: Our new test for NIPD of DMD/BMD has been shown to be accurate and reliable during initial stages of validation. It is also feasible for implementation into clinical service. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. Abstract : What's Already Known About This Topic? Recent research has shown that non‐invasive prenatal diagnosis for some single gene disorders is possible, and there is some implementation into clinical practice for the detection or exclusion of the paternal allele. However, this is not yet available for definitive diagnosis of X‐linked conditions. What Does This Study Add? We have developed an accurate and feasible test for the non‐invasive prenatal diagnosis of Duchenne and Becker muscular dystrophies. Early validation data have proven that the method could potentially be implemented into clinical practice.