Noninvasive paternal exclusion testing for cystic fibrosis in the first five to eight weeks of gestation

Sci Rep. 2018 Oct 29;8(1):15941. doi: 10.1038/s41598-018-34396-6.

Abstract

Prenatal genetic testing is not generally applicable to the very early stages of pregnancy (prior to week 8 gestation), a time period that is crucial to pregnant couples with high risk for transmission of genetic disease to their fetus. Therefore, we developed a new ultra-sensitive targeted next generation sequencing method for noninvasive haplotype-based paternal allele exclusion testing of the cystic fibrosis-associated gene, CFTR. This new method was compared to a conventional library prep and sequencing analysis method and all test results were validated by amniotic fluid testing at later stages of pregnancy. Out of 7 enrolled couples, who provided at least two blood samples (at least one week apart) for noninvasive CFTR testing, a result was obtained for 6 fetuses. Using the new hypersensitive method, all six couples (100%) received a correct diagnosis for the paternal allele as opposed to 3/6 (50%) when tested with the conventional strategy. Among 4 couples who provided just one early pregnancy blood draw for analysis, diagnosis was possible in one fetus, but only using the ultra-sensitive method. Thus, we describe a novel noninvasive CFTR screening method which demonstrates unprecedented fetal allele typing accuracy in the earliest stages of pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cystic Fibrosis / diagnosis*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • DNA / chemistry
  • DNA / isolation & purification
  • DNA / metabolism
  • Female
  • Genetic Testing / methods*
  • Genotype
  • Gestational Age
  • Haplotypes
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Sequence Analysis, DNA

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator
  • DNA