CHROMOSOME BREAKAGE IN INDIVIDUALS WITH SINGLE-CELL STRUCTURAL-ABERRATIONS AND HABITUAL ABORTIONS

The rate of spontaneous and methotrexate (MTX)-induced chromosome breakage was studied in individuals with a history of habitual abortions in whom a structural chromosomal aberration was found in a single cell during routine cytogenetic analysis. Twelve such individuals were selected because they were not under the influence of any known mutagenic factor such as smoking, alcohol, medication and apparent irradiation; they were compared to 12 age- and sex-matched control parents. A detailed statistical analysis revealed that the spontaneous and MTX-induced chromosome breakage was significantly increased in the abortion group. The MTX-induced breakage rate was especially elevated in the women of the abortion group

Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21

The trials performed worldwide toward noninvasive prenatal diagnosis (NIPD) of Down's syndrome (or trisomy 21) have shown the commercial and medical potential of NIPD compared to the currently used invasive prenatal diagnostic procedures. Extensive investigation of methylation differences between the mother and the fetus has led to the identification of differentially methylated regions (DMRs). In this study, we present a strategy using the methylated DNA immunoprecipitation (MeDiP) methodology in combination with real-time quantitative PCR (qPCR) to achieve fetal chromosome dosage assessment, which can be performed noninvasively through the analysis of fetal-specific DMRs. We achieved noninvasive prenatal detection of trisomy 21 by determining the methylation ratio of normal and trisomy 21 cases for each tested fetal-specific DMR present in maternal peripheral blood, followed by further statistical analysis. The application of this fetal-specific methylation ratio approach provided correct diagnosis of 14 trisomy 21 and 26 normal cases. © 2011 Nature America, Inc. All rights reserved

Mapping interleukin enhancer binding factor 2 gene (ILF2) to human chromosome 1 (1q11-qter and 1p11-p12) by polymerase chain reaction amplification of human-rodent somatic cell hybrid DNA templates

Interleukin-2 (IL-2) is the first lymphokine secreted following T cell activation. Several transcription factors regulate IL-2 gene expression, including the nuclear factor of activated T cells (NFAT). NFAT acts at the antigen receptor response element-2 (ARRE-2) sequence in the IL-2 enhancer and is the nuclear target of T cell stimulation signals and the immunosuppressant drugs cyclosporine and FK506, which are potent inhibitors of IL-2 gene transcription. NFAT has been cloned and found to consist of two subunits, NF45 (ILF2) and NF90 (ILF3). This communication reports the assignment of NF45, interleukin enhancer binding factor 2 gene (ILF2), to human chromosome 1 (1q11-qter and 1p11-p12) by polymerase chain reaction (PCR) amplification of ILF2-specific DNA sequences from well-characterized human-rodent somatic cell hybrid DNA

Mandibulofacial dysostosis (Treacher-Collins syndrome) in the fetus: Novel association with pectus carinatum in a molecularly confirmed case and review of the fetal phenotype

BACKGROUND: Treacher Collins syndrome is the most common mandibulofacial dysostosis of autosomal dominant or, rarely, recessive inheritance. Affected fetuses may be identified by prenatal ultrasound or diagnosed at autopsy in case of perinatal death or pregnancy termination. METHODS: We describe the ultrasonographic, autopsy, and molecular findings in a 25-week-gestation affected fetus, and review the clinical, prenatal, and postmortem findings in 15 previously reported fetal and perinatal cases. RESULTS: A nearly complete spectrum of the typical facial characteristics can be present by the early second trimester of gestation, including subtle defects such as lower eyelid colobomas. Mandibular hypoplasia and bilateral auricle defects were constant findings in the affected fetal population. Downslanting palpebral fissures were the second more common feature, followed by midface hypoplasia, polyhydramnios, and ocular defects. Association with Pierre Robin sequence was common (38%) in the reviewed series. Previously unreported pectus carinatum was noted in our case bearing a heterozygous TCOF1 mutation. Other unique reported findings include salivary gland hyperplasia, single umbilical artery, and tracheo-esophageal fistula, all in molecularly unconfirmed cases. CONCLUSION: Treacher Collins syndrome can be prenatally detected by ultrasound and should be included in the wide range of genetic syndromes that can be diagnosed at perinatal autopsy. Affected fetuses tend to have a more severe phenotype than living patients. The reported association of Treacher Collins syndrome type 1 with pectus carinatum expands the phenotype, provides information on genotype-phenotype correlation, and suggests possible pathogenetic interactions between neural crest cell disorders and the formation of the sternum that merit investigation. © 2013 Wiley Periodicals, Inc

A simple and effective approach for detecting maternal cell contamination in molecular prenatal diagnosis

The presence of maternal cells in fetal samples constitutes a serious potential source for prenatal misdiagnosis, Here we present our approach for detecting maternal cell contamination (MCC) at prenatal diagnosis for eight monogenic disorders (autosomal recessive: beta-thalassaemia, sickle-cell anaemia, cystic fibrosis, prelingual deafness’ autosomal dominant: achondroplasia, Huntington disease, myotonic dystrophy. neurofibromatosis type 1: X-linked: spinobulbar muscular atrophy). Our aim was to apply a simple and low-cost approach. which would easily and accurately provide information on the fetal tissue MCC status. MCC testing was applied to cases of recessive inheritance adhere the primary mutation screening of the fetus revealed the presence of the maternal mutation. to cases concerning dominant inheritance and to cases of multiple gestation, The potential presence of maternal cells was determined by the amplification of the 3’-HVR/APO B. D1S80, THO1 and VNTRI of vWf polymorphic loci, which have previously demonstrated high heterozygosity in Caucasians. Among 135 prenatal diagnoses. 44 finally needed to be tested for MCC (32.6%). MCC was detected in four cases, where DNA was isolated directly from chorionic villi samples (CVS). and in one case with DNA isolated directly from amniotic fluid (AF). In almost 90%, of cases a simple test of one polymorphic locus provided sufficient information about MCC. The choice of the appropriate locus is therefore essential, while the simultaneous screening of both parents provides the means for distinguishing non-informative sites about MCC. Copyright (C) 2002 John Wiley Sons, Ltd

Clinical and molecular description of a fetus in prenatal diagnosis with a rare de novo ring 10 and deletions of 12.59Mb in 10p15.3-p14 and 4.22Mb in 10q26.3

Ring chromosomes are rare cytogenetic findings and are mostly associated with an abnormal phenotype. We report on the prenatal diagnosis of a ring chromosome 10 in a fetus in which talipes equinovarus was incidentally found during routine obstetric ultrasound at 22 weeks of gestation. Amniocentesis was undertaken and cytogenetic analysis revealed a de novo non-mosaic apparently stable ring chromosome 10 replacing one of the two homologs. Multiplex Ligation-dependent Probe Amplification (MLPA) revealed subtelomeric deletions in both the short and long arm of chromosome 10. Analysis with high resolution micro-array based comparative genomic hybridization (array-CGH), defined the ring chromosome as del 10p15.3-p14 (12.59. Mb in size) and del 10q26.3 (4.22. Mb in size) and revealed the genes that are deleted. After elected termination of the pregnancy at 27th week of gestation a detailed autopsy of the fetus allowed for genotype-phenotype correlations. To our knowledge, this is the first case of a de novo ring chromosome 10 which is reported during prenatal diagnosis and is thoroughly investigated with array CGH and autopsy study. © 2011 Elsevier Masson SAS

Clinical and molecular description of a fetus in prenatal diagnosis with a rare de novo ring 10 and deletions of 12.59 Mb in 10p15.3-p14 and 4.22 Mb in 10q26.3

Ring chromosomes are rare cytogenetic findings and are mostly associated with an abnormal phenotype. We report on the prenatal diagnosis of a ring chromosome 10 in a fetus in which talipes equinovarus was incidentally found during routine obstetric ultrasound at 22 weeks of gestation. Amniocentesis was undertaken and cytogenetic analysis revealed a de novo non-mosaic apparently stable ring chromosome 10 replacing one of the two homologs. Multiplex Ligation-dependent Probe Amplification (MLPA) revealed subtelomeric deletions in both the short and long arm of chromosome 10. Analysis with high resolution micro-array based comparative genomic hybridization (array-CGH), defined the ring chromosome as del 10p15.3-p14 (12.59 Mb in size) and del 10q26.3 (4.22 Mb in size) and revealed the genes that are deleted. After elected termination of the pregnancy at 27th week of gestation a detailed autopsy of the fetus allowed for genotype-phenotype correlations. To our knowledge, this is the first case of a de novo ring chromosome 10 which is reported during prenatal diagnosis and is thoroughly investigated with array CGH and autopsy study. (C) 2011 Elsevier Masson SAS. All rights reserved