Characterization of a prenatally assessed de novo supernumerary minute ring chromosome 20 in a phenotypically normal male

<p>Abstract</p> <p>Background</p> <p>The heterogeneous group of small supernumerary marker chromosomes (sSMCs) presents serious counseling problems, especially if they are present de novo and diagnosed prenatally. The incidence has been estimated at 1 in 1000 prenatal samples. We present a case of mosaic sSMC diagnosed prenatally after amniocentesis. The sSMC was characterized by various molecular cytogenetic techniques and determined to be a r(20) chromosome. After genetic counseling, the parents decided to continue the pregnancy, and a boy with minor phenotypic variants was born after 39 weeks of pregnancy. The case is compared with four other cases of prenatally detected r(20) mosaicism.</p> <p>Results</p> <p>Here we describe a 3 months old male child with normal pre- and postnatal development and with a de novo ring supernumerary marker chromosome in amniocytes cultures. Using new fluorescence in situ hybridization (FISH) techniques, three distinguishable sSMCs (cryptic mosaicism), all derived from chromosome 20, were observed, including ring and minute chromosomes. This heterogeneity was impossible to detect by the conventional G-banding technique or conventional FISH technique that were used before the application of new FISH techniques (subcentromere-specific multicolor-FISH [subcenM-FISH]) and a probe, specific for the 20p12.2 band. The sSMC present in 25% of the cells was present as r(20)(::p12.2~12.3->q11.1::)<abbrgrp><abbr bid="B5">5</abbr></abbrgrp>/r(20;20)(::p12.1->q11.1::q11.1 >p12.1::)<abbrgrp><abbr bid="B2">2</abbr></abbrgrp>/min(20;20)(:p12.1->q11.1::q11.1->p12.1:)<abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. The final karyotype was 47,XY,+r(20)[25%]/46,XY[75%].</p> <p>Conclusion</p> <p>We emphasize the importance of application of molecular cytogenetics in a prenatally diagnostic laboratory and description of more cases to enable a better genetic counseling and risk evaluation.</p

Prenatal diagnosis services in Greece

The report presents the available prenatal diagnosis (PND) services in Greece. PND for chromosomal anomalies after amniocentesis was initiated in 1976 and became gradually widely accepted. Chorionic villus sampling was introduced in 1983. Approximately 6,500 women undergo PND for chromosomal anomalies annually, most of them for advanced maternal age. 700 cases are also tested prenatally each year for haemoglobinopathies. The study describes the PND services available in the country, the procedures currently used, the impact of prenatal testing on the prevention of genetic diseases and the legal issues concerning PND in Greece

Awareness and use of prenatal diagnosis among Greek women: A national survey

The prevention of genetic diseases through prenatal diagnosis depends to a large extent on the awareness and acceptance of available methods by the public. A national survey was conducted among Greek women in order to explore their attitudes towards and their use of prenatal diagnosis in relation to their lifestyle. The survey was originally addressed to 3000 Greek women 18-65 years of age. Using as a criterion having a child 5 years old or younger, 350 women were eligible for the study. It was noted that 52 per cent of the respondents were adequately informed; while 48 per cent had either superficial knowledge of the subject or no knowledge at all. Amniocentesis was the method that most women were familiar with. The majority said that they were informed by their doctors and the media, and 13 per cent of the participants had prenatal diagnosis during a previous pregnancy. Twenty-two per cent of those who were not tested were over 35 years of age at the time of pregnancy. There was a significant positive correlation between awareness and acceptance of prenatal diagnosis, on the one hand, and the social, educational and financial profile of the women, on the other. Women aware of prenatal diagnosis adhered more closely to a healthy lifestyle and lived a family-centred life. (C) 1998 John Wiley &amp; Sons, Ltd

AUTOSOMAL FOLATE SENSITIVE FRAGILE SITES IN NORMAL AND MENTALLY-RETARDED INDIVIDUALS IN GREECE

The frequencies of autosomal folate sensitive fragile sites were compared in populations of mentally retarded fra(X) negative (N = 220) and normal children (N = 76) in Greece. In addition, the frequency of autosomal fragile sites was studied in 20 known fra(X) children in order to test if the fra(X) syndrome is associated with general chromosome instability. The frequencies of both common and rare autosomal fragile sites did not differ significantly between the mentally retarded and the normal children, although the rate of expression was considerably higher in the retarded group. Autosomal fragile sites were not increased in the fra(X) patients. Fra(3)(p14) was by far the most frequent one in all groups. The frequency of fra(6)(q26) was found to be considerably higher among the mentally retarded children, this difference being almost statistically significant. Further cytogenetic studies of normal and retarded individuals are required in order to elucidate this point further

Improved specificity of NRBC detection in chorionic villus sample supernatant fluids using anti-zeta and anti-epsilon monoclonal antibodies

Objective: Fetal erythrocytes leak from fetal capillaries at the time of chorionic villus sampling (CVS). it has been reported that in approximately 60% of CVS cases fetal nucleated red blood cells (NRBC) can be isolated from the supernatant fluid by immunophenotyping with monoclonal antibody (Ab) against the gamma-chain of fetal hemoglobin and used as an additional source for confirmation of the fetal karyotype. However, the increased prevalence of beta-thalassemia mutations in countries such as Greece results in many pregnant women who produce gamma-positive cells. This makes it difficult to distinguish between the fetal and maternal origin of the NRBC. Use of Abs against embryonic hemoglobin chains zeta and epsilon may increase specificity for fetal NRBC detection. Methods: Mouse monoclonal Abs against Hb-zeta and Hb-epsilon were used in order to examine if specificity for fetal NRBC detection in CVS supernatant fluids could be improved. 41 samples were studied using anti-zeta and 20 using anti-zeta monoclonal Abs. Results: Anti-zeta or anti-epsilon positive erythrocytes were, respectively, identified in 52 of 61 CVS samples and anti-zeta or anti-epsilon positive NRBC were present in all cases. The mean number of Hb-positive erythrocytes identified with the anti-zeta Ab was 58 and the mean number of NRBC 29. The mean number of anti-g positive erythrocytes was 30 and of NRBC 23. FISH with X and Y chromosome specific probes was performed in 26 cases and the results were concordant with the CVS karyotype. Statistical analysis using the correlation test showed that anti-zeta and anti-epsilon were more specific for the detection of embryonic NRBCs. Conclusions: Since embryonic monoclonal Abs show increased specificity, they should be preferentially used for NRBC detection in CVS supernatant fluids. Furthermore, the increased specificity of anti-zeta and anti-epsilon Abs may considerably improve prenatal diagnosis from fetal cells isolated from maternal circulation

The molecular basis of HbH disease in Greece

Summary. Globin gene mapping in 16 Greek individuals with HbH disease and their parents has demonstrated the occurrence of several HbH genotypes brought about by the interaction of two α+‐thalassaemia and two α+‐thalassaemia haplotypes. Eight of the 16 patients had the genotype Med/ ‐α3.7, four the genotype –(a)20.5/–α3.7 and three the genotype Med/aαT. In one patient the restriction data are consistent with two possible genotypes aαT/αTor /aαT. It is demonstrated that HbH disease in Greece is heterogeneous, with the deletion haplotypes Med and –α3.7 being more prevalent than the ‐(a)20.5 and non‐deletion (ααT) haplotypes. Copyright © 1986, Wiley Blackwell. All rights reserve