PubMed Health⌕ Search

Biomedical subjects

K Sermon

Publications and source records attributed to K Sermon.

At least 37 records · Page 2Linked to original sources
PubMed2000

ESHRE preimplantation genetic diagnosis (PGD) consortium: data collection II (May 2000).

In 1997, the ESHRE PGD Consortium was formed as part of the ESHRE Special Interest Group on Reproductive Genetics, in order to undertake a long-term study of the efficacy and clinical outcome of preimplantation genetic diagnosis (PGD). In December 1999, the first PGD Consortium report was published discussing referrals of 323 couples, 392 PGD cycles and 82 pregnancies and 79 children born. In the second round of data collection, contributing centres were asked to send in data from their PGD activities before January 1997, as well as from 1st October 1998 until 1st May 2000, in order to have as complete as possible an overview of PGD practices in these centres. A further 563 referrals were sent in as well as 926 PGD cycles, and data on 89 pregnancies (including seven pregnancies ongoing from the previous group) and 83 children were collected. This has led to a considerable amount of cumulative data being acquired: over a period of 7 years (the oldest PGD cycle reported dates from 1994), referral data on 886 couples, cycle data on 1318 PGD cycles and data on 163 pregnancies and 162 babies were collected. In all, these data are encouraging: they show first, that the practice of PGD is becoming more and more established, and an increasing number of different applications is emerging; and second, that collecting these data is worthwhile, as they will be a valuable source of information for all those involved, e.g. in counselling patients and interacting with governmental bodies.

Aneuploidy↗
PubMed2000

Preimplantation genetic diagnosis for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common defect in fatty acid oxidation. The disease is inherited in an autosomal recessive fashion (carrier frequency around 1 in 70) and probably affects as many as 1 in 10000 new-borns. Affected children usually present within the two first years of life with recurrent episodes of hypoketotic hypoglycaemia and lethargy leading to death in approximately 25% of the cases. One mutation (c985A-->G) accounts for approximately 90% of the carrier chromosomes. We developed a preimplantation genetic diagnosis (PGD) strategy for MCAD for a couple who had already lost two affected children. When tested on heterozygous lymphoblasts, the amplification efficiency was 67 out of 71 (94%) and the allele drop-out rate was 0 out of 67. The patient became pregnant after one PGD cycle during which two embryos were replaced. The twin pregnancy was checked by chorionic villus sampling (CVS) and was shown to be unaffected. The twins have been born and are healthy.

Acyl-CoA Dehydrogenase↗
PubMed1999

Preimplantation genetic diagnosis of Marfan syndrome with the use of fluorescent polymerase chain reaction and the Automated Laser Fluorescence DNA Sequencer.

OBJECTIVE: To develop and apply clinical preimplantation genetic diagnosis (PGD) for Marfan syndrome. DESIGN: Case report. SETTING: Centers for medical genetics and reproductive medicine in university hospitals. PATIENT(S): One couple in which the husband was affected with Marfan syndrome. INTERVENTION(S): The couple underwent three intracytoplasmic sperm injection cycles. MAIN OUTCOME MEASURE(S): The correct diagnosis was obtained for embryos in three PGD cycles. RESULT(S): Although all the PGD cycles were followed by ET, no pregnancy ensued. CONCLUSION(S): This assay can provide a reliable and accurate preimplantation diagnosis of Marfan syndrome.

Adult↗
PubMed1999

ESHRE Preimplantation Genetic Diagnosis (PGD) Consortium: preliminary assessment of data from January 1997 to September 1998. ESHRE PGD Consortium Steering Committee.

The first clinical application of preimplantation genetic diagnosis (PGD) was reported almost a decade ago. Since then, the range of genetic defects that can be detected at single cell level has increased dramatically. At the 13th Annual Meeting of ESHRE in Edinburgh in 1997, a PGD Consortium was formed to undertake the first systematic and long-term study of the efficacy and clinical outcome of PGD. We report here the first data collection covering the period of January 1997 to September 1998. Referral data on 323 couples have been collected for a variety of monogenic and chromosomal disorders, providing information about which patients, at risk for which genetic diseases, are interested in PGD. Data were collected on 392 PGD cycles, resulting in 302 embryo transfers and 66 clinical pregnancies. Because of the importance of follow-up of the children born after PGD, participating centres were asked to contribute data on the pregnancies achieved and the children born after PGD since the start of their PGD programme. Data on 82 pregnancies and 110 fetal sacs were collected, and information was available on 79 children. Finally, biopsy, fluorescence in-situ hybridization and polymerase chain reaction protocols were collected, clearly showing that no consensus exists on technical aspects such as which culture medium to use, and emphasizing the role the PGD Consortium could play in setting up guidelines for good laboratory practice. In conclusion, it is clear that the effort of gathering data on PGD cycles is worthwhile and will be continued in the future, preferably using electronic data collection.

Female↗
PubMed1999

Fluorescent PCR and automated fragment analysis in preimplantation genetic diagnosis for 21-hydroxylase deficiency in congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease which is most often caused by a deficiency in steroid 21-hydroxylase. The disease is characterized by a range of impaired adrenal cortisol and aldosterone synthesis combined with an increased androgen synthesis. These metabolic abnormalities lead to an inability to conserve sodium and virilization of females. The most common mutation causing the severe form of CAH is a conversion of an A or C at nucleotide (nt) 656 to a G in the second intron of the steroid 21-hydroxylase gene (CYP21) causing aberrant splicing of mRNA. A couple was referred to our centre for preimplantation genetic diagnosis (PGD) for 21-hydroxylase deficiency in CAH. A PGD was set up to detect the nt656 A/C-->G mutation using fluorescent polymerase chain reaction (PCR) and subsequent restriction enzyme digestion and fragment analysis on an automated sequencer. Using DNA or single cells from the father, the normal allele could not be amplified. Non-amplification of the normal allele has been previously described in asymptomatic carriers, therefore the PCR was further developed using heterozygous lymphoblasts from the mother. The PCR was shown to be highly efficient (96% amplification), accurate (0% contamination) and reliable (0% allelic drop-out). The couple started PGD treatment and the second PGD cycle resulted in a twin pregnancy. The genotype of the fetuses was determined in our laboratory using chorionic villus sampling material using the method described here. Both fetuses were shown to be heterozygous carriers of the mutation, and two healthy girls were born.

Adrenal Hyperplasia, Congenital↗
PubMed1999

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

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 allele. Our candidate-patient population, as well as two clinical preimplantation genetic diagnosis (PGD) cycles which led to a pregnancy with an unaffected fetus, are presented in this paper.

Adult↗
PubMed1998

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

Huntington's disease (HD) is an autosomal dominant disease characterized by motor disturbance, cognitive loss and psychiatric manifestations, starting between the fourth and the fifth decade, followed by death within 10-20 years of onset of the disease. The disease-causing mutation is an expansion of a CAG triplet repeat at the 5' coding end of the Huntington gene. We have developed a single-cell PCR assay for the HD gene in order to propose preimplantation genetic diagnosis (PGD) for the couples at risk. We present here our first results with our first nine PGD cycles and also discuss the behaviour of the disease-causing expansion in pre-implantation embryos.

Adult↗
PubMed1998

Successful preimplantation genetic diagnosis is related to the number of available cumulus-oocyte complexes.

The inheritance pattern of monogenic inheritable disorders influences the proportion of unaffected embryos after preimplantation genetic diagnosis (PGD). We aimed to investigate the influence of the number of cumulus-oocyte complexes (COC) on the outcome after PGD. Eighty-four cycles of 47 couples were included in our analysis. All couples were at risk of transmitting autosomal recessive, autosomal dominant, X-linked single gene disorders or sexaneuploidies to their offspring. One PGD cycle was carried out for a Yq-deletion of the man. The correlation between the numbers of COC and biopsied embryos and between the numbers of COC and unaffected embryos was highly significant (P <0.05). A pregnancy occurred in 15 cycles and a minimum of six COC were needed to achieve a pregnancy. Thirteen pregnancies were observed in cycles with at least 9 COC. The transfer rate and number of transferred embryos per cycle in the subgroups with <9 COC and > or =9 COC were significantly higher in the latter. Although pregnancy rates did not differ significantly between the two subgroups (probably due to the low number of pregnancies), our data indicate that it is justifiable to cancel PGD cycles in which it is expected that <6 COC will be retrieved and that the couple should be informed about the poor prognosis if <9 COC are retrieved.

Cystic Fibrosis↗
PubMed1998

Clinical experience with preimplantation genetic diagnosis and intracytoplasmic sperm injection.

Preimplantation genetic diagnosis (PGD) is a novel procedure whose use may be considered to obtain a very early prenatal diagnosis for couples at risk for transmitting genetic diseases. Using the polymerase chain reaction (PCR) or fluorescence in-situ hybridization (FISH) the genotype or the sex of biopsied cleavage-stage embryos obtained after in-vitro fertilization can be determined and selected embryos can then be transferred. In-vitro fertilization with intracytoplasmic sperm injection is the method of choice to obtain embryos to be analysed through PCR to reduce contamination by residual sperm DNA. In our 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%. One of the six morphologically normal children born, who is still alive and doing well, weighed 850 g after birth at 25 weeks following a complicated triplet pregnancy. More experience is needed to correctly evaluate the efficiency and safety of this novel technique as well as to determine its place in the prevention of genetic disease.

Adult↗
PubMed1998

Pregnancy after preimplantation genetic diagnosis for Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth (CMT) disease type 1A is an autosomal dominant peripheral neuropathy characterized by slow progressive distal muscle wasting and weakness, and decreased nerve conduction velocities. Most CMT1A cases (>98%) are caused by a duplication of a 1.5 Mb region on the short arm of chromosome 17 containing the PMP22 gene. A couple with a previous history of CMT followed by termination of pregnancy was referred to our centre for preimplantation genetic diagnosis (PGD). The husband carries the CMT1A duplication which can be detected by polymerase chain reaction (PCR) analysis using polymorphic (CA)n markers localized within the duplication. PCR amplification of genomic DNA of the parents-to-be with one of the two primers labelled with fluorescein, followed by automated laser fluorescence (ALF) gel electrophoresis of the amplified fragments allows the distinction between both genotypes. Embryos obtained after intracytoplasmic sperm injection (ICSI) were evaluated for the presence of the normal allele of the father. PCR with single Epstein-Barr virus-transformed lymphoblasts and blastomeres resulted in 91.4 and 93.5% amplification efficiency respectively, whereas none of the blank controls gave a positive signal. Allele drop-out (ADO) was observed in eight out of 32 lymphoblasts (25%) or in five out of 21 blastomeres (23.8%). However, within this set-up ADO will never lead to transfer of an affected embryo. A first ICSI-PGD cycle did not result in embryo transfer for the patient. A second cycle involved 10 mature oocytes of which eight were fertilized, resulting in five embryos for biopsy. Two unaffected embryos were available for transfer and resulted in a singleton pregnancy. The genotype of the fetus has been confirmed healthy by chorionic villus sampling.

Alleles↗
PubMed1998

Fluorescent PCR and automated fragment analysis for the clinical application of preimplantation genetic diagnosis of myotonic dystrophy (Steinert's disease).

Myotonic dystrophy (DM), or Steinert's disease, is an autosomal dominant disease characterized by myotonia, muscular weakness and atrophy, as well as lens opacities, cardiomyopathy and mild endocrine changes. The gene for DM located on 19q contains a triplet repeat at the 3' end of the gene. In DM patients, this repeat is found to be expanded. We have previously described a preimplantation genetic diagnosis (PGD) for DM using polymerase chain reaction (PCR) followed by conventional analysis on ethidium bromide-stained gels. The major drawback of this system was that allelic dropout occurred in >20% of the cells, leading to the loss of healthy embryos for transfer. To resolve this problem, we developed a PGD for DM using fluorescent PCR followed by fragment analysis on an automated DNA sequencer and made a comparison between the conventional PCR described earlier and fluorescent PCR, which turned out to be superior in accuracy and efficiency. Three PGD cycles were performed using fluorescent PCR and are described here.

Adult↗
PubMed1997

Preimplantation genetic diagnosis: current status and new developments.

Preimplantation genetic diagnosis (PGD) is a very early form of prenatal diagnosis aimed at eliminating embryos carrying serious genetic diseases before implantation. To this end, two major technologies are in use: the polymerase chain reaction (PCR) for monogenic diseases and fluorescent in-situ hybridization (FISH) for chromosomal aberrations. In this review, a number of problems arising from the use of these technologies, as well as their possible solutions and new developments, are discussed. Concerning PCR, the phenomenon of allelic drop-out, as well as methods to reduce this problem, such as fluorescent PCR, are described. The advantages and disadvantages of sperm separation by flow cytometry as an adjunct to sex determination for the avoidance of X-linked disease are discussed. The application of FISH for aneuploidy detection is commented upon and the advances in cell recycling, in which PCR and FISH are combined, are analysed. Finally, diseases for which PGD is currently possible are summarized.

Alleles↗
PubMed1997

Clinical application of preimplantation diagnosis for myotonic dystrophy.

Myotonic dystrophy (DM) or Steinert's disease is a progressive autosomal dominant disease characterized by increasing muscle weakness, myotonia, cataracts, and endocrine abnormalities such as diabetes and testicular atrophy. The gene for DM was cloned in 1992 and the mutation was shown to be an expanded trinucleotide (CTG) repeat. A polymerase chain reaction (PCR)-based assay was described soon after that would allow (prenatal) diagnosis of the disease. Based on these PCR assays, we have developed a method for carrying out single-cell PCR for DM. In preimplantation diagnosis, embryos obtained in vitro are checked for the presence or absence of a disease, after which only embryos shown to be free of the disease under consideration are returned to the mother. A single-cell assay was developed for preimplantation diagnosis in couples where one of the parents is afflicted with DM. Twenty intracytoplasmic sperm injection (ICSI) cycles were carried out in eight patients and between one and four embryos were replaced in 17 out of 20 cycles. Two of the patients became pregnant and have had prenatal diagnosis which has confirmed that they are unaffected.

Adult↗
PubMed1996

Review: preimplantation diagnosis of inherited disease.

Preimplantation diagnosis of inherited diseases has become possible with the techniques of in vitro fertilization, blastomere biopsy of the 6- to 10-cell embryo and DNA analysis of the single blastomeres. Disease-free embryos are selected for transfer to the uterus, thereby avoiding the need for termination of a fetus diagnosed as affected in prenatal diagnosis in the first or early-second trimester of pregnancy. The genetic indications for preimplantation diagnosis are theoretically the same as for prenatal diagnosis, but the defects must be detectable by the polymerase chain reaction. For X-linked recessive diseases, fluorescence in situ hybridization can be used as an alternative for the selection of female embryos. So far almost 40 healthy children have been born worldwide after preimplantation diagnosis for genetic disease. The possibilities and limitations of preimplantation diagnosis, especially in prevention of inherited disease, are discussed in this review.

Alleles↗
PubMed1996

Adaptation of the primer extension preamplification (PEP) reaction for preimplantation diagnosis: single blastomere analysis using short PEP protocols.

Primer extension preamplification (PEP) was first described as a method for whole genome amplification, starting from a single cell, originally a spermatozoon, in order to perform genetic recombination studies. Its usefulness for preimplantation diagnosis was shown soon after; the only drawback was the length of the procedure (> 14 h). We have developed a shorter PEP protocol for single human blastomeres, enabling us to examine several genetic loci of interest in human genetic diseases with a good amplification efficiency.

Blastomeres↗
PubMed1995

Amplification of exon 11 of the gene for the alpha-chain of beta-N-acetylhexosaminidase in single human blastomeres.

OBJECTIVE: To evaluate the possibility of using polymerase chain reaction (PCR) technology for preimplantation diagnosis for Tay-Sachs disease. DESIGN: Polymerase chain reaction on single human blastomeres. SETTING: Bad quality embryos from IVF analyzed in an academic research genetics lab. INTERVENTIONS: Patients underwent standard IVF procedures as infertility treatment. RESULTS: Amplification was seen in 89.5% of the blastomeres; only one blank was contaminated. CONCLUSION: The technique of PCR on single blastomeres is ready to be used in clinical preimplantation diagnosis for Tay-Sachs disease.

Base Sequence↗