Clinical Service Delivery of Noninvasive Prenatal Diagnosis by Relative Haplotype Dosage for Single-Gene Disorders

J Mol Diagn. 2020 Sep;22(9):1151-1161. doi: 10.1016/j.jmoldx.2020.06.001. Epub 2020 Jun 15.

Abstract

A relative haplotype dosage (RHDO)-based method was developed and implemented into routine clinical practice for noninvasive prenatal diagnosis (NIPD) of multiple single-gene disorders: spinal muscular atrophy, Duchenne and Becker muscular dystrophies, and cystic fibrosis. This article describes the experiences of the first 152 pregnancies to have NIPD by RHDO as part of a routine clinical service. Provision of results within a clinically useful time frame (mean, 11 calendar days) was shown to be possible, with a very low failure rate (4%), none being due to a technical failure. Where follow-up confirmatory testing was performed for audit purposes, 100% concordance was seen with the NIPD result, and no discrepancies have been reported. The robust performance of the assay, together with high sensitivity and specificity, demonstrates that NIPD by RHDO is feasible for use in a clinical setting.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Cell-Free Nucleic Acids / genetics
  • Cystic Fibrosis / diagnosis*
  • Cystic Fibrosis / genetics*
  • Diagnostic Tests, Routine / methods
  • Feasibility Studies
  • Female
  • Fetal Diseases / diagnosis*
  • Fetal Diseases / genetics*
  • Follow-Up Studies
  • Haplotypes*
  • Humans
  • Male
  • Muscular Dystrophy, Duchenne / diagnosis*
  • Muscular Dystrophy, Duchenne / genetics*
  • Noninvasive Prenatal Testing / methods*
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Retrospective Studies
  • Sensitivity and Specificity
  • Spinal Muscular Atrophies of Childhood / diagnosis*
  • Spinal Muscular Atrophies of Childhood / genetics*

Substances

  • Cell-Free Nucleic Acids