title: Non-invasive prenatal diagnosis of Duchenne and Becker muscular dystrophies by relative haplotype dosage.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Parks
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Samantha
authors.initials: S
authors.lastname: Court
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Siobhan
authors.initials: S
authors.lastname: Cleary
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Samuel
authors.initials: S
authors.lastname: Clokie
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Hewitt
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Denise
authors.initials: D
authors.lastname: Williams
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Trevor
authors.initials: T
authors.lastname: Cole
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: MacDonald
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Griffiths
authors.affiliation: West Midlands Regional Genetics Laboratory, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Allen
mesh_terms: D016022:Case-Control Studies; D002474:Cell-Free System; D004247:DNA / Q000097:blood; D016189:Dystrophin / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods*; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D062145:Maternal Serum Screening Tests / Q000379:methods*; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy
chemical_list: C484258:DMD protein, human; D016189:Dystrophin; D005819:Genetic Markers; D004247:DNA
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