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Biomedical subjects

E Flori

Publications and source records attributed to E Flori.

At least 19 recordsLinked to original sources
PubMed2006

Phenotype in X chromosome rearrangements: pitfalls of X inactivation study.

OBJECTIVE: X inactivation pattern in X chromosome rearrangements usually favor the less unbalanced cells. It is correlated to a normal phenotype, small size or infertility. We studied the correlation between phenotype and X inactivation ratio in patients with X structural anomalies. PATIENTS AND METHODS: During the 1999-2005 period, 12 X chromosome rearrangements, including three prenatal cases, were diagnosed in the Laboratoire de Cytogénétique of Strasbourg. In seven cases, X inactivation ratio could be assessed by late replication or methylation assay. RESULTS: In three of seven cases (del Xp, dup Xp, t(X;A)), X inactivation ratio and phenotype were consistent. The four other cases showed discrepancies between phenotype and X inactivation pattern: mental retardation and dysmorphism in a case of balanced X-autosome translocation, schizophrenia and autism in two cases of XX maleness and MLS syndrome (microphthalmia with linear skin defects) in a case of Xp(21.3-pter) deletion. CONCLUSION: Discrepancies between X inactivation ratio and phenotype are not rare and can be due to gene disruption, position effect, complex microrearrangements, variable pattern of X inactivation in different tissues or fortuitous association. In this context, the prognostic value of X inactivation study in prenatal diagnosis will be discussed.

Abnormalities, Multiple↗
PubMed2004

Circulating cell-free fetal DNA in maternal serum appears to originate from cyto- and syncytio-trophoblastic cells. Case report.

Circulating cell-free fetal DNA in maternal serum offers an early and non-invasive method for prenatal diagnosis, but the origin of this DNA is still unknown. We report the absence of the SRY gene in maternal serum of a pregnant woman despite male genitalia at ultrasound. The karyotype was 45,X after direct trophoblast analysis and 45,X/46,Xidic(Yp) after culture and in all fetal tissues studied. Due to the absence of the SRY sequence in maternal blood and in the cytotrophoblast, we presume that free fetal DNA in this case originates from trophoblastic cells. As the case presented here is exceptional, it only has a minor impact on the accuracy of fetal sex determination by maternal serum analysis, but highlights the importance of and the necessity for the complementary ultrasonographic control.

DNA↗
PubMed2004

Prenatal diagnosis of a true fetal tetraploidy in direct and cultured chorionic villi.

Prenatal diagnosis of a true fetal tetraploidy in direct and cultured chorionic villi: Tetraploidy is characterized by four complete sets of chromosomes (4n= 92). Although it has been frequently reported in spontaneous abortions, tetraploidy is extremely rare in term pregnancy. Most of late surviving patients are diploid/tetraploid mosaics and present severe mental and physical impairment. Up to date, only five tetraploidies were ascertained in the prenatal stage in amniocytes and/or fetal blood lymphocytes. No one has been reported in chorionic villi probably because tetraploidy is generally considered in this tissue as a false positive result due to confined placental mosaicism (CPM) or placental culture artefacts. We report here on a case of tetraploidy detected in chorionic villi because of fetal cystic hygroma. We discuss the reliability of this diagnosis and propose guidelines in the follow-up of tetraploidies detected after chorionic villus sampling (CVS). Thus a misdiagnosis of this poor condition will be avoided at best and an appropriate genetic counseling will be given to the parents.

Amniocentesis↗
PubMed2003

Recurrent neural tube defects associated with partial trisomy 2p22-pter: report of two siblings and review of the literature.

We report on two male siblings with partial trisomy 2p22-pter and partial monosomy 15q26-qter resulting from a maternally derived translocation t(2;15)(p22;q26). Both fetuses had different neural tube defects (craniorachischisis in the first fetus and anencephaly in the second fetus) which were detected by sonographic examination at the end of the first trimester of pregnancy. This report demonstrates the importance of chromosomal analysis in the etiologic exploration of neural tube defects and supports the importance of 2p24 triplication in neural tube development.

Anencephaly↗
PubMed2000

Costello syndrome: report of six patients including one with an embryonal rhabdomyosarcoma.

UNLABELLED: Costello syndrome was first described in 1971. Besides papillomata, which were part of the initial description, patients tends to develop benign tumours of ectodermal origin. Aetiology is yet unknown but it is supposed to be the result of a sporadic dominant mutation. We report six patients with typical clinical findings and emphasise the importance of cardiac manifestations and the tendency to develop tumours. One patient developed an embryonal rhabdomyosarcoma, the occurrence of which has been reported twice before in patients with Costello syndrome. CONCLUSION: There might be a causal link between the development of rare tumours and this genetic disorder which may provide a new clue concerning the identification of the gene involved in Costello syndrome.

Cardiomyopathy, Hypertrophic↗
PubMed1998

Preparing for preimplantation genetic diagnosis in France.

Preimplantation genetic diagnosis (PGD) allows the detection of genetic defects before implantation, thus circumventing the possible need for abortion. France's current legislation allows the practice of PGD under certain circumstances which include the prerequisite agreement of the French health authority. Unfortunately, to enact the pending 'bioethical law', voted in July 1994, a decree still needs to be published. So, for the moment, although we know that PGD should be authorized, its practice is currently impossible in France. In order to prepare for licensing, we are setting up the relevant technologies, by performing biopsy on mouse embryos and fluorescent in-situ hybridization (FISH) experiments on human lymphoblast cells. We briefly describe the French legal situation with regard to PGD and the work we have performed in this context to obtain the licensing to offer PGD to patients. After a period of preparation, 95.9% of biopsies were successful and up to 95.4% of the biopsied blastomeres were properly spread onto slides. Biopsied and control mouse embryos were reimplanted into pseudopregnant females and similar birth rates were obtained (34.4 and 30.9% respectively). In these experiments we noticed a birth delay of 12-24 h for the biopsied embryos compared with the controls. Furthermore, scanning electron microscopy of the biopsied embryos allowed assessment of the hole made by the Tyrode's acid. By intercrossing adults derived from biopsied embryos for two successive generations, it was shown that the biopsy did not generate defects affecting their reproductive ability. FISH experiments were performed using specific probes for chromosomes X, Y and 1 on nuclei spread by a conventional protocol or a Tween/HCl blastomere spreading protocol; in the latter case, slides with 1-5 cells were prepared. A similar percentage of correct X,Y,1,1 signal was obtained from all three types of spreading, varying from 85.5 to 89.9%.

Animals↗
PubMed1996

Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease.

Hirschsprung disease (HSCR, aganglionic megacolon) is a frequent congenital malformation regarded as a multigenic neurocristopathy. Two susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene and the endothelin B receptor (EDNRB) gene. Hitherto however, homozygosity for EDNRB mutations accounted for the HSCR-Waardenburg syndrome (WS) association. Here, we report heterozygous EDNRB missense mutations (G57S, R319W and P383L) in isolated HSCR. These data might suggest that EDNRB mutations could be dosage sensitive: heterozygosity would predispose to isolated HSCR with incomplete penetrance, while homozygosity would result in more complex neurocristopathies associating HSCR and WS features. In addition, the present data give further support to the role of the endothelin-signalling pathway in the development of neural crest-derived enteric neurons.

Female↗
PubMed1996

Deletion of Asn281 in the alpha-subunit of the human insulin receptor causes constitutive activation of the receptor and insulin desensitization.

We studied the structure and function of the insulin receptor (IR) in two sisters with leprechaunism. The patients had inherited alterations in the IR gene and were compound heterozygotes. Their paternal IR allele carried a major deletion, including exons 10-13, which shifted the reading frame and introduced a premature chain termination codon in the IR sequence. This allele was expressed at a very low level in cultured fibroblasts (< 10% of total IR messenger ribonucleic acid content) and encoded a truncated protein lacking transmembrane and tyrosine kinase domains. The maternal IR allele was deleted of 3 bp in exon 3, causing the loss of Asn281 in the alpha-subunit. This allele generated levels of IR messenger ribonucleic acid and cell surface receptors similar to those seen in control fibroblasts. However, IRs from patients' cells had impaired insulin binding and exhibited in vivo and in vitro constitutive activation of autophosphorylation and tyrosine kinase activity. As a result of this IR-preactivated state, the cells were desensitized to insulin stimulation of glycogen and DNA syntheses. These findings strongly suggest that Asn281 of the IR alpha-subunit plays a critical role in the inhibitory constraint exerted by the extracellular alpha-subunit over the intracellular kinase activity.

Amino Acid Sequence↗
PubMed1995

Frequent occurrence of the CFTR intron 8 (TG)n 5T allele in men with congenital bilateral absence of the vas deferens.

Isolated congenital bilateral absence of the vas deferens (CBAVD) is an autosomal recessive disorder which has recently been shown to be associated with cystic fibrosis (CF) mutations. As part of an effort to understanding the genetic basis of this disorder, we have analysed the entire coding sequence and all the intron/exon boundaries of the cystic fibrosis transmembrane conductance regulator (CFTR) gene from 45 azoospermic individuals with this phenotype. We were able to detect a CFTR gene defect in 86% of chromosomes from these subjects. In addition to identifying 9 novel CFTR gene mutations, we found that a surprisingly high proportion (84%) of men with CBAVD who are heterozygous for a CF mutation carry the intron 8 polypyrimidine 5T CFTR allele on one chromosome. We hypothesise that this tight and significant (p < 10(-6)) linkage reflects the very mild impact of this mutation on CFTR gene expression. Although genetic heterogeneity cannot be excluded, CBAVD patients in whom no CFTR mutation has been detected are likely to harbour additional unidentified mild mutations. These observations have implications for the genetic counselling of CBAVD patients and CF families, and couples undergoing in vitro fertilisation procedures.

Alleles↗
PubMed1994

Supernumerary chromosomes and spermatogenesis in a human male carrier.

A 57-year-old patient was referred because of primary sterility. Spermogram and testicular histology showed moderate oligospermia and irregular hypospermatogenesis. Karyotypic analysis revealed the presence of a metacentric supernumerary chromosome. Synaptonemal complex analysis using the surface-spreading technique was undertaken to study the meiotic behaviour of the extra chromosome during the pachytene stages. The relationship of the extra chromosome to the infertility of the carrier is discussed.

Chromosome Aberrations↗
PubMed1991

Mosaic 46,XY/92,XXYY,del(5)(q13 q34) in an adult lymphoblastic leukemia.

Usually the chromosome anomalies encountered in ALL are modal number abnormalities (hyperdiploidy or hypodiploidy) and structural anomalies such as t(8;14), t(11;14), t(9;22), t(1;19) and del(6p). The 5q- syndrome is mainly associated with myelodysplastic syndromes and with ANLL (M1, M2, M3). We report the case of a patient presenting with a mosaic karyotype 46,XY/92,XXYY,del(5)(q13 q34) in the following proportion 1/3 normal mitoses and 2/3 tetraploid mitoses.

Aged↗
PubMed1988

Interstitial deletion of chromosome 15: two cases.

Two cases of interstitial deletion of chromosome 15 with similar clinical features are presented. In one case, assay of hexosaminidase A enabled us to confirm that the structural gene is located between 15q22 and 15q25 and that it is included in the deletion.

Abnormalities, Multiple↗