Expanded carrier screening and preimplantation genetic diagnosis in a couple who delivered a baby affected with congenital factor VII deficiency

BMC Med Genet. 2018 Jan 24;19(1):15. doi: 10.1186/s12881-018-0525-9.

Abstract

Background: Preimplantation genetic diagnosis (PGD) is a powerful tool for preventing the transmission of Mendelian disorders from generation to generation. However, PGD only can identify monogenically inherited diseases, but not other potential monogenic pathologies. We aimed to use PGD to deliver a healthy baby without congenital FVII deficiency or other common Mendelian diseases in a couple in which both individuals carried a deleterious mutation in the F7 gene.

Methods: After both members of the couple were confirmed to be carriers of the F7 gene mutation by Sanger sequencing, expanded carrier screening (ECS) for 623 recessive inheritance diseases was performed to detect pathological mutations in other genes. PGD and preimplantational genetic screening (PGS) were employed to exclude monogenic disorders and aneuploidy for their embryos.

Results: ECS using targeted capture sequencing technology revealed that the couple carried the heterozygous disease-causative mutations c.3659C > T (p.Thr1220Ile) and c.3209G > A (p.Arg1070Gln) in the CFTR gene. After PGD and PGS, one of their embryos that was free of congenital FVII deficiency, cystic fibrosis (CF) and aneuploidy was transferred, resulting in the birth of a healthy 3200 g male infant.

Conclusion: We successfully implemented PGD for congenital FVII deficiency and PGD after ECS to exclude CF for the first time to the best of our knowledge. Our work significantly improved the reproductive outcome for the couple and provides a clear example of the use of ECS combined with PGD to avoid the delivery of offspring affected not only by identified monogenically inherited diseases but also by other potential monogenic pathologies and aneuploidy.

Keywords: Congenital FVII deficiency; Cystic fibrosis; Expanded carrier screening; Preimplantation genetic diagnosis; Preimplantational genetic screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / prevention & control
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Factor VII / genetics
  • Factor VII / metabolism
  • Factor VII Deficiency / diagnosis*
  • Factor VII Deficiency / genetics*
  • Factor VII Deficiency / prevention & control
  • Female
  • Fertilization in Vitro
  • Gene Deletion
  • Genes, Recessive
  • Genetic Diseases, Inborn / diagnosis
  • Genetic Diseases, Inborn / genetics
  • Genetic Diseases, Inborn / prevention & control
  • Genetic Predisposition to Disease
  • Genetic Testing*
  • Humans
  • Infant
  • Male
  • Pedigree
  • Pregnancy
  • Pregnancy Outcome
  • Preimplantation Diagnosis*
  • Sequence Analysis, DNA
  • Whole Genome Sequencing

Substances

  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Factor VII