Preimplantation diagnosis for fragile X syndrome based on the detection of the non‐expanded paternal and maternal CGG

  title={Preimplantation diagnosis for fragile X syndrome based on the detection of the non‐expanded paternal and maternal CGG},
  author={Karen Sermon and Sara Seneca and Anna Vanderfaeillie and Willy Lissens and Hubert Joris and Mark Vandervorst and Andr{\'e} C. van Steirteghem and Inge Liebaers},
  journal={Prenatal Diagnosis},
Fragile X syndrome is the most common monogenic cause of mental retardation in boys. It is always characterized clinically by moderate mental retardation and often by a long face with large everted ears and macro‐orchidism. The causal mutation is an expansion of a CGG triplet repeat in a 5′ exon of the FMR‐1 gene in Xq27.3. We report here for the first time a method for preimplantation genetic diagnosis (PGD) for fragile X syndrome based on the amplification of the CGG triplet in the normal… 

Improving preimplantation genetic diagnosis for Fragile X syndrome: two new powerful single-round multiplex indirect and direct tests

Two new single-cell, single-round multiplex PCR for indirect and direct diagnosis of FraX on biopsied embryos are described, robustness of the diagnosis is improved and the loss of potentially healthy embryos (because they are non-diagnosed or mis diagnosed) is limited.

Preimplantation genetic diagnosis of the fragile X syndrome by use of linked polymorphic markers

Use of polymorphic markers flanking the mutation to track the normal and premutation carrying maternal chromosomes in preimplantation embryos is accurate and applicable to a larger number of patients at risk of transmitting fragile X to their offspring.

Preimplantation genetic diagnosis for fragile X syndrome: is there increased transmission of abnormal FMR1 alleles among female heterozygotes?

This study was undertaken to evaluate the performance of preimplantation genetic diagnosis (PGD) for fragile X, and to assess the transmission rate of the abnormal FMR1 alleles in this setting.

Clinical and Technical Overview of Preimplantation Genetic Diagnosis for Fragile X Syndrome: Experience at the University Hospital Virgen del Rocio in Spain

The PGD Program applied to Fragile X syndrome resulted in the birth of 3 unaffected babies of FXS for 2 of the 11 couples, supporting that, despite the important drawbacks of PGD for FXS, efforts should be devoted in offering this reproductive option to the affected families.

Genetic prenatal and preimplantation diagnosis of trinucleotide repeat disorders

  • N. DeanA. Ao
  • Medicine
    Expert review of neurotherapeutics
  • 2002
The history, present status and future of genetic antenatal diagnosis for the trinucleotide repeat disorders, including Huntington′s disease, Fragile X syndrome and myotonic dystrophy are examined.

Preimplantation genetic diagnosis for fragile Xa syndrome: difficult but not impossible.

PGD for fragile Xa is feasible for a number of couples and women with a premutation are at increased risk of premature ovarian failure, so Fragile Xa premutation carriers are advised not to postpone reproduction for too long.

FMR1 CGG repeat expansion mutation detection and linked haplotype analysis for reliable and accurate preimplantation genetic diagnosis of fragile X syndrome

FMR1 TP-PCR reliably detects presence of expansion mutations and obviates reliance on informative normal alleles for determining expansion status in female embryos, and together with multi-marker haplotyping and gender determination, misdiagnosis and diagnostic ambiguity due to allele dropout is minimised, and couple-specific assay customisation can be avoided.

Multiple displacement amplification for preimplantation genetic diagnosis of fragile X syndrome.

Data indicate that MDA and fluorescent PCR with four loci can be successfully applied to PGD for fragile X syndrome and advanced methods for amplification of minuscule amounts of DNA could improve the sensitivity and reliability ofPGD for complicated single gene disorders.

Preimplantation genetic diagnosis for single gene disorders: experience with five single gene disorders

The data demonstrate the successful strategy of using multiplex PCR to simultaneously amplify the mutation site and a polymorphic locus, fluorescent PCR technology to achieve greater sensitivity, and two‐cell biopsy to increase the efficiency and success of diagnoses.



The full mutation in the FMR–1 gene of male fragile X patients is absent in their sperm

Study of FMR–1 in sperm of four male fragile X patients showed that only the premutation was present in their sperm, although they had a full mutation in peripheral lymphocytes, which might suggest that expansion of the premutations to the full mutations in FMR-1 does not occur in meiosis but in a postzygotic stage.

Transition from premutation to full mutation in fragile X syndrome is likely to be prezygotic.

Analysis of tissues from affected fetuses indicate that such a putative postzygotic transition would have to occur very early in embryogenesis and most likely before determination of germ cell lineage, and it is proposed that this is strong, albeit indirect evidence against a postzyGotic transition to FM.

Preimplantation diagnosis for Huntington's disease (HD): clinical application and analysis of the HD expansion in affected embryos

A single‐cell PCR assay for the HD gene is developed in order to propose preimplantation genetic diagnosis (PGD) for the couples at risk of Huntington's disease and the behaviour of the disease‐causing expansion in pre‐im implantation embryos is discussed.

Inheritance of the fragile X syndrome: size of the fragile X premutation is a major determinant of the transition to full mutation.

The fragile X mental retardation syndrome is caused by unstable expansion of a CGG repeat and direct detection of the mutations is used to characterise large families who illustrate the wide variation in penetrance which has been observed in different sibships (a feature often called the Sherman paradox).

DNA methylation represses FMR-1 transcription in fragile X syndrome.

Preliminary prenatal diagnosis of a male fetus with fragile X syndrome is reported by utilizing molecular differences and indicates that the abnormal methylation of the FMR-1 CpG-island is responsible for the absence of F MRM-1 transcription and suggests that the methylation may be acquired early in embryogenesis.

Clinical application of preimplantation diagnosis for myotonic dystrophy

A single‐cell assay was developed for preimplantation diagnosis in couples where one of the parents is afflicted with DM and two patients became pregnant and have had prenatal diagnosis which has confirmed that they are unaffected.

Clinical experience with preimplantation genetic diagnosis and intracytoplasmic sperm injection.

In the series of 61 PGD cycles for 29 couples at risk over a period of 4 years the ongoing pregnancy rate per cycle was 15%, per transfer 19% and per patient 31%.

Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome

expression of the fragile X syndrome appears to result from a two-step mutation as well as a highly localized methylation, and can easily be detected regardless of sex or phenotypic expression.