Preimplantation genetic diagnosis of X-linked diseases examined by indirect linkage analysis

Bratisl Lek Listy. 2015;116(9):542-6. doi: 10.4149/bll_2015_103.

Abstract

Background: Many centers of assisted reproduction in the Czech Republic offer preimplantation genetic diagnosis with fluorescent in situ hybridization (FISH) to couples requiring preimplantation genetic diagnosis (PGD) of X-linked diseases. However, this process results in discarding all male embryos and is not able to distinguish a carrier or healthy female embryo in X-linked recessive disorders.

Objectives: The main aim of this study was to summarize a six-year period of PGD of X-linked monogenic diseases using indirect linkage analysis.

Methods and results: We wanted to accentuate the advantage indirect analysis of PGD using multiple displacement amplification (MDA) followed by short tandem repeat (STR) analysis. We present forty-six PGD cycles, including pre-case haplotyping (PGH) panel, for fifteen X-linked diseases. Embryo transfer was made thirty-eight times and gravidity was confirmed in thirteen female probands with a success rate of pregnancy calculated at 42 %.

Conclusions: PGD procedure using MDA amplification followed by STR analysis provides help in identifying genetic defects within embryos prior to implantation. The reliability of the method was also supported by high pregnancy rate compared to other publications, which commonly achieved a 30-35 % success rate (Tab. 2, Fig. 1, Ref. 33).

Keywords: X-linked inheritance; haplotype analysis.; indirect diagnosis; single gene mutation.

Publication types

  • Clinical Study

MeSH terms

  • Adult
  • Cohort Studies
  • Czech Republic
  • Embryo Transfer*
  • Female
  • Fertilization in Vitro*
  • Genetic Diseases, X-Linked / diagnosis*
  • Genetic Diseases, X-Linked / genetics
  • Genetic Diseases, X-Linked / prevention & control
  • Genetic Linkage*
  • Haplotypes
  • Humans
  • Male
  • Microsatellite Repeats
  • Mutation
  • Nucleic Acid Amplification Techniques
  • Pregnancy
  • Pregnancy Rate
  • Preimplantation Diagnosis / methods*
  • Reproducibility of Results
  • Retrospective Studies