bluuebunny/crossref_metadata_2025 huggingface dataset:
United states survey on chromosome mosaicism and pseudomosaicism in prenatal diagnosis
Authors: Hsu Lillian Y. F. , Perlis Theresa E.
Published: March 2007

The survey of the incidence of chromosome mosaicism and pseudomosaicism detected in prenatal diagnosis included data from approximately 60 000 genetic amniocenteses in the United States. There were 59 participating cytogenetic laboratories nationwide. The overall incidence of chromosome mosaicism was 0.25 per cent (range of 0–0.89 per cent). The average frequency of pseudomosaicism involving multiple cells or clones was 0.7 per cent (range of 0–11.21 per cent). The frequency of single cell or clone pseudomosaicism was 2.47 per cent (range of 0–11.49 per cent). In cases of pseudomosaicism with trisomy, the most frequently involved chromosome was number 2; occurrence rates of trisomies 7,X,9,17 and 20 were also relatively high. In cases of pseudomosaicism with structural abnormalities, this survey showed an association between relative chromosome size and the frequency of involvement in structural rearrangement. Data on a total of 185 cases of chromosome mosaicism collected in this survey as well as from other documented sources showed 89 cases involved an autosome, 13 cases a sex chromosome, and 23 a marker chromosome. The frequency of noticeable phenotypic abnormalities was highest (37.8 per cent) in the autosomal mosaics and lowest (10.5 per cent) in the sex chromosome mosaics. The average rate for cytogenetic confirmation was 70 per cent.
Tests appropriate for the prenatal diagnosis of ataxia telangiectasia
Authors: Schwartz S. , Flannery D. B. , Cohen M. M.
Published: March 2007

A fetus ‘at‐risk’ for ataxia telangiectasia (A‐T) was monitored prenatally by several approaches which, in concert, might yield information of diagnostic value: measurement of amniotic fluid AFP levels; the clastogenic potential of ‘at‐risk’ amniotic fluid; and cytogenic evaluation of fetal amniocytes. All three parameters proved negative and normality, based primarily on the chromosomal study of fetal cells, was therefore presumed. This conclusion was confirmed shortly after birth by normal serum AFP levels and the lack of increased spontaneous or clastogen‐induced chromosome breakage in the infant's cells. Based on previous observations from four normal and one affected fetus, the coordination of these techniques provides adequate methodology for the antenatal assessment of the phenotypes associated with A‐T.
A case of partial sirenomelia and possible vitamin A teratogenesis
Authors: Von Lennep E. , El Khazen N. , De Pierreux G. , Amy J. J. , Rodesch F. , Van Regemorter N.
Published: March 2007

Prenatal echographical findings of a partial sirenomelic fetus are described. An attempt was made to terminate pregnancy by administration of prostaglandin F2a, but uterine rupture occurred. The teratogenic role of vitamin A ingested by the mother in the penconceptional period is discussed.
Utilization of prenatal cytogenetic diagnosis in women of advanced maternal age in Australia, 1979–1982
Authors: Bell J. A. , Pearn J. , Cohen G. , Ford J. , Halliday J. , Martin N. , Mulcahy M. , Purvis‐Smith S. , Sutherland G.
Published: March 2007

This paper reports the results of a complete national survey to measure utilization rates of prenatal cytogenetic diagnosis (P.C.D.) in women of advanced maternal age in Australia. P.C.D. has been available throughout Australia for the last decade. Every laboratory in Australia providing a P.C.D. service for the years 1979–1982 took part in this study. Utilization rates (both National and State rates) by ages of mothers, are presented. Big interstate differences exist. The 1982 National P.C.D. utilization rate for pregnant women who were 40 years of age and over was 38.8 per cent, and this rate has shown an average annual increase of 9 per cent. In those four States which offered P.C.D. to pregnant women of 35 years or over the median utilization rate was 20 per cent. These Australian rates indicate an under‐utilization of P.C.D. services with (in 1982) 50–80 per cent of ‘at risk’ women not being tested. Factors which influence this are discussed.
Evaluation of a prenatal screening procedure for β‐thalassaemia carriers in a chinese populationbased on the mean corpuscular volume (MCV)
Authors: Ghosh A. , Woo J. S. K. , Wan C. W. , Machenry C. , Wong V. , Ma H. K. , Chan Vivian , Chan T. K.
Published: March 2007

Haemoglobin A2 (HbA2) levels were determined on 25 β‐thalassaemia carriers by the microcolumn method and were found to range from 4.5–7.2 per cent (mean 5.2±0.82 S.D.). The haemoglobin level (Hb), mean corpuscular volume (MCV), plasma ferritin and HbA2 levels were measured on a further 299 cconsecutive Chinese pregnant women at a gestation of less than 24 weeks. 18 patients (6 per cent) had HbA2 level greater than 4.5 per cent and were diagnosed to be β‐thalassaemic carriers. It was observed that all these patients had a MCV below 75 fl. If this level is selected in a screening procedure based on measurement of MCV alone all β‐thalassaemia carriers could be detected and 11 per cent of the population screened would require HbA2 estimation. At a lower cut‐off level of 70 fl, 8 per cent of the population screened wouid require HbA2 measurement (a decrease of 27 per cent) but the detection rate will be lowered considerably (83 per cent). The high false positive rate at all cut‐off levels of MCV was largely due to the prevalence of iron deficiency anaemia in the population. Estimation of plasma ferritin level in patients with low MCV will reduce this false positive rate, but there will be a considerable delay in diagnosis in patients with concomitant iron deficiency and β‐thalassaemia. The presence of iron deficiency in β‐thalassaemia carriers did not reduce their HbA2 level below the diagnostic range in this study. Measurement of Hb level did not appear to be useful as a screening method since one third of the β‐thalassaemia carriers had a Hb level over 11 g/dl. The validity of the MCV cut‐off levels derived from the first part of the study was assessed in screening a larger population. 61 β‐thalassaemia carriers (6 per cent) were detected out of 1166 patients screened. This incidence was not significantly different from the first part of the study. All these 61 patients had a MCV less than 75 ml.

It was concluded that a two‐step screening policy, based on MCV measurement followed by HbA2 estimation when the MCV value is less than 75 fl, is suitable for our population. It is efficient, straight forward with excellent sensitivity and required less time and effort for both laboratory staff and clinicians.
Prenatal diagnosis of cystic fibrosis: I. Prospective study of 51 pregnancies
Authors: Muller F. , Berg S. , Frot J. C. , Boué J. , Boué A.
Published: March 2007

A prenatal diagnosis was performed in 51 pregnancies with a 1‐in‐4 risk of having a child with cystic fibrosis. The criteria for determining an affected fetus were based on the results of alkaline phosphatase (ALP) residual activity after inhibition by phenylalanine and by homoarginine, of total ALP activity, and of gamma‐glutamyltranspeptidase (GGTP) activity in the amniotic fluid taken between 16 and 19 weeks of pregnancy.

The chromosomal analysis of amniotic fluid cells showed trisomy 13 in one case which was excluded from the analysis of biochemical assays. The biochemical assays were in the normal ranges in the amniotic fluid of 35 pregnancies: 26 have reached term and a normal infant has been born, 9 are still in progress.

A deficiency of the ALP phenylalanine‐inhibitable form, depressed values of total ALP and GGTP were observed in the amniotic fluid of 15 pregnancies: one pregnancy went to term and the infant had CF, in 14 cases the pregnancy was terminated, and meconium ileus was observed in ten of these cases.

It was observed that the changes towards abnormal values became more significant with advancing gestational age and that 18 weeks appeared to be the optimum time for diagnostic amniocentesis.
Prenatal diagnosis and perinatal management of a fetal ovarian cyst
Authors: Holzgreve Wolfgang , Winde Bernd , Willital G. H. , Beller Fritz K.
Published: March 2007

A case of a prenatally diagnosed fetal ovarian cyst is presented. The pregnancy was complicated only by polyhydramnios, and some degree of fetal bowel obstruction could be recognized on sonogram.

The newborn was delivered vaginally in the 39th week of pregnancy, and the cyst was removed by laparotomy on the day of the delivery.

The etiology of this rare fetal condition is unknown.
Further examples of trisomy‐20 mosaicism in amniotic cell cultures
Authors: Grewal M. S. , Ridler M. A. C. , Barber J. C. K.
Published: March 2007

Amniotic fluid cultures from two patients showed trisomy‐20 mosaicism. No trisomy‐20 cells were found in a normal full term infant and in multiple tissue biopsies and fetal blood from a fetus after a termination of pregnancy. No definitive advice is yet possible for parents where trisomy‐20 amniotic cell mosaicism is detected. Fetoscopy and fetal blood sampling are of no value and termination of pregnancy is not indicated by empirical evidence. Preferential trophoblastic non‐disjunction (Kalousek and Dill, 1983) is discussed as a possible partial explanation for the variable occurrence and distribution of this type of mosaicism.
Testosterone levels in midtrimester maternal and fetal plasma and amniotic fluid
Authors: Rodeck C. H. , Gill D. , Rosenberg D. A. , Collins W. P.
Published: March 2007

Testosterone was measured in maternal plasma (58 samples), amniotic fluid (71 samples) and fetal plasma (55 samples) in 79 patients between 15 and 23 weeks' gestation. Maternal plasma testosterone levels were unrelated to fetal sex. Amniotic fluid testosterone was significantly higher in male than female fetuses but did not reliably predict fetal sex. A correct diagnosis of fetal sex was made by testosterone assay of pure fetal plasma in 39 out of 40 males and in 15 out of 15 females using 1.70 nmol/1 as the cut‐off value. This investigation is not the method of choice for routine fetal sexing but may be of value in fetuses suspected of having certain endocrine disorders.
Third trimester ultrasound diagnosis of intestinal atresia following clinical evidence of polyhydramnios
Authors: Filkins Karen , Russo Joseph , Flowers William
Published: March 2007

Five cases of intestinal atresia were diagnosed using real‐time ultrasonography following clinical evidence of polyhydramnios. No correlation was noted between ultrasound findings and the severity of the lesions. Two of the five babies died at 35 and 77 days respectively. Prematurity and presence of other abnormalities were factors in the deaths.
Cystic hygroma: Prenatal diagnosis and genetic counselling
Authors: Marchese C. , Savin E. , Dragone E. , Carozzi F. , De Marchi M. , Campogrande M. , Dolfin G. C. , Pagliano G. , Viora E. , Carbonara A.
Published: March 2007

Six cases of cystic hygromas detected during second trimester ultrasound examination are reported: 4 fetuses (67 per cent) had a 45, X karyotype, 1 fetus had trisomy 18, 1 fetus had a normal karyotype (46,XX) and at autopsy multiple anomalies were observed. In the latter case the family history suggested an autosomal recessive pattern of inheritance. In order to reach a definite diagnosis and give proper genetic counselling when a fetus is found to have cystic hygroma, a fetal karyotype as well as a family and reproductive history should be obtained.
Prenatal diagnosis of the fragile‐X in male monozygotic twins: Discordant expression of the fragile site in amniocytes
Authors: Rocchi M. , Pecile V. , Archidiacono N. , Monni G. , Dumez Y. , Filippi G.
Published: March 2007

A prenatal diagnosis of the fragile‐X syndrome in monozygotic male twins is reported. The expression of the fragile site was discordant in amniotic cells. Fetal blood and, after therapeutic abortion, skin fibroblasts were positive in both fetuses. Our data suggest that great care should be taken when using amniocytes for prenatal diagnosis of the fragile‐X syndrome.
Sonographic demonstration of fetal sacrococcygeal teratoma
Authors: Holzgreve Wolfgang , Mahony Barry S. , Glick Philip L. , Filly Roy A. , Harrison Michael R. , Delorimier Alfred A. , Holzgreve Alfred C. , Muller Klaus M. , Callen Peter W. , Anderson Robert L. , Golbus Mitchell S.
Published: March 2007

Six cases of sonographically diagnosed fetal sacrococcygeal teratoma (SCT) are presented and illustrate the variable features of fetal SCT. The sonographic findings assisted the parents and perinatal team in making decisions, and in two of the cases the children survived after elective Cesarean section and prompt neonatal resection of the tumors. None of the patients showed signs of malignant degeneration of the teratoma or metastases. Fetal SCT no longer should be considered a uniformly fatal condition. The literature on sacrococcygeal teratoma detected after birth indicates that the mortality rate is correlated with the degree of extension of the tumor. Therefore, the classification of sonographically diagnosed fetal SCT according to its size and position is important for decisions regarding pregnancy management.
The fetal behavioural states: An ultrasonic study
Authors: Arduini D. , Rizzo G. , Giorlandino C. , Vizzone A. , Nava S. , Dell'Acqua S. , Valensise H. , Romanini C.
Published: March 2007

In order to accurately detect the fetal behavioural state, we simultaneously measured fetal heart rate and multiple fetal activities in 27 healthy pregnant women at 38 to 40 weeks of gestation.

We ultrasonically identified gross body movements, breathing movements and micturition. Analysis of fetal heart rate allowed us to distinguish two different patterns of fetal behaviour: active and quiet phases. The frequency distribution of the analysed fetal events was significantly different in these two phases. These data suggest that a complete biophysical profile of the fetus is effective in differentiating behavioural states and may improve the predictive accuracy of fetal heart rate analysis alone.
Direct fetal chromosome studies from chorionic villi
Authors: Flori E. , Nisand I. , Flori J. , Dellenbach P. , Ruch J. V.
Published: March 2007

An easy and reproducible technique for direct fetal chromosome analysis after chorionic biopsy is described. Very high colchicine concentration and rehydratation of the fixed villi are the two original points of this method.
High resolution chromosomes from first trimester trophoblast cultures
Authors: Søndergaard Finn , Kristensen Merete , Tommerup Niels
Published: March 2007

A simple method for obtaining prometaphase chromosomes from cultured first trimester cells involves the addition of BrdU and FdU 11 h before harvest and ethidium bromide 1.5 h before harvest. High resolution R‐banding is obtained by acridine orange staining.
Exclusion of citrullinaemia in the first trimester of pregnancy by direct assay of argininosuccinate synthetase in chorionic villi
Authors: Christensen E. , Brandt N. J. , Philip J. , Bang J.
Published: March 2007

Citrullinaemia was presumed to be excluded in a fetus at risk by the direct assay of argininosuccinate synthetase in chorionic villi. The diagnosis was confirmed after amniocentesis by normal argininosuccinate synthetase activity in the cultured amniotic fluid cells and by a normal citrulline concentration in the amniotic fluid. The prediction of a normal fetus was confirmed at term by the birth of a non‐citrullinaemic boy.
Spontaneous abortion after amniocentesis in women with a history of spontaneous abortion
Authors: Esrig Stella M. , Leonardi Donna E.
Published: March 2007

The incidence of spontaneous abortion after amniocentesis (19 to 28 weeks gestation) in women who have had previous spontaneous abortions is compared with the rate in women who have not had previous spontaneous abortions. The outcome of the pregnancy after amniocentesis and the previous history of spontaneous abortion is reported for 691 pregnancies. The rate of spontaneous abortion after amniocentesis was found to be significantly higher in women who had one or more previous spontaneous abortions, 12/238 (5 per cent), than in women who did not, 6/453 (1.3 per cent). In women who reported two or more previous spontaneous abortions, the rate was 7/81 (8.6 per cent). No statistically significant effect of maternal age or gravidity was detected. The incidence of spontaneous abortion after amniocentesis was greater in the three weeks following the procedure (three for each of the three weeks) than in the subsequent seven weeks (nine for seven weeks).
Early prenatal diagnosis of genetic microcephaly
Authors: The H. Nguyen , Pescia G. , Deonna Th , Bakarić O.
Published: March 2007

We report a new case of prenatal diagnosis of recessive microcephaly by ultrasound examination allowing termination of pregnancy at 25 weeks gestation.
Distinguishing hygroma and amniotic fluid
Authors: Brock David J. H. , Barron Lilias , Bedgood David , Rodeck Charles
Published: March 2007

Fluid from cystic hygromata can be distinguished from amniotic fluid by measurement of alkaline phosphatase (ALP) isoenzymes. The former has a serum‐type ALP, made up largely of the liver/bone/kidney isoenzyme and virtually no intestinal isoenzyme. Second trimester amniotic fluid ALP contains approximately 80 per cent intestinal isoenzyme.
Prenatal diagnosis by chorionic villus sampling: Lessons of the first 600 cases
Authors: Hogge W. A. , Schonberg S. A. , Golbus M. S.
Published: March 2007

Chorionic villus sampling (CVS) has emerged as a first trimester alternative to amniocentesis for the prenatal detection of genetic disorders. We report our experience in 600 consecutive CVS procedures to better delineate the safety, efficacy and reliability of this new method of prenatal diagnosis. Adequate samples were obtained at the initial visit in 97 per cent of the cases, and successful cultures were established in 98.7 per cent of these patients. Chromosome abnormalities were detected in 5.9 per cent of those pregnancies tested because of advanced maternal age (≥ 35 years). A discrepancy between the villus karyotype and that of the fetus was found in 2.0 per cent of cases, and most commonly consisted of mosaicism in the villus sample for a chromosomal abnormality that was not found in fetal samples. The risk of spontaneous abortion following the procedure was 6.3 per cent. We conclude that chorionic villus sampling is an acceptably safe and reliable procedure, but further investigation is needed before it can become an established technique in prenatal diagnosis.
Prenatal diagnosis of Mohr syndrome by ultrasonography
Authors: Iaccarino M. , Lonardo F. , Giugliano M. , Della Bruna Mimma
Published: March 2007

A case of prenatal diagnosis of Mohr syndrome is presented. The ultrasound examination was indicated by the previous birth of an affected brother. The need for genetic counselling is stressed, when polydactyly is observed accidentally at ultrasound examination during pregnancy.
The use of amniotic FSH levels in resolving a discrepancy between fetal chromosomal and phenotypic sex
Authors: Dalprà L. , Castagni M. , Nocera G. , Tibiletti M. G. , Riboni G. , Agosti S.
Published: March 2007

We report a case in which a discrepancy emerged between the prenatal diagnosis of female chromosomal sex and male sex at ultrasound examination. The FSH dosage performed on an amniotic fluid sample previously stored confirmed the male phenotype of the fetus. The effectiveness of the AF‐FSH level dosage in prenatal diagnosis was taken into consideration.
The impact of prenatal diagnosis on the occurrence of chromosome abnormalities
Authors: Bell Judith , Hilden Jørgen , Bowling Francis , Pearn John , Brownlea Arthur , Martina Nicole
Published: March 2007

From the public health point of view, several formal attempts have been made to measure the impact of prenatal diagnosis (PND) on the incidence of Down's Syndrome (DS), but the results have varied widely. The impact of PND (reduction in the birth rate of chromosomally abnormal neonates) is related to utilization rates but quantitative estimates of this have not been established. In a three‐year (1981–1983) total population study from Queensland, Australia, we present results to measure the impact of a voluntary PND programme on the birth incidence of DS, and also other chromosomally abnormal births. Utilization rates for the PND service were 15·5 per cent in that population of mothers 35 years and over. Numbers and rates of all cases of chromosomal abnormalities are presented, subclassified by type of diagnosis–‐either by PND or by clinical diagnosis after birth. For the total population, 7·3 per cent of cases of DS were detected prenatally, and 15·4 per cent of all chromosome abnormalities. (A method for measuring the impact of PND is described.) Using this in conjunction with our demographic data, we estimate that with a 15 per cent utilization rate of PND by older mothers, 14 per cent of DS births can be prevented in this age group, or a 5 per cent overall reduction can be achieved if mothers of all ages are considered. One index–‐the ratio of the percentage of DS births which are preventable compared with the population utilization rates of PND–‐has potential for widespread use. Queensland data for this ratio is 0·34, a figure consistent with that from other studies. Thus a 3·5 per cent drop in the overall DS birth rate may be expected for each 10 per cent increase in the utilization rates of PND for mothers of 35 years and over. A diagram is presented which may serve as a model for improved data collection and better impact estimates in the future.
Biochemical examination of fetal skin biopsy specimens obtained by fetoscopy: Use of the method for analysis of keratins and filaggrin
Authors: Dale Beverly A. , Perry Tracy B. , Holbrook Karen A. , Hamilton Emily F. , Senikas Vyta
Published: March 2007

This paper describes a method for biochemical analysis of proteins from fetal skin biopsy samples. The method has wide potential application for diagnosis of disorders with a known protein abnormality detectable by protein staining or a specific antibody. Analysis requires a single 1 mm biopsy, is rapid (2 days) and extremely sensitive. In the present study, fetal skin biopsies from normal fetuses and a fetus at risk for lamellar ichthyosis were obtained. The epidermis or hairs with attached follicular cells were dissected from the remaining skin. Proteins were extracted and separated by SDS‐polyacrylamide gel electrophoresis. Proteins from duplicate gels were transferred to nitrocellulose and immunostained for the acidic and basic keratins and for the keratin filament associated protein, filaggrin, using monoclonal antibodies. All samples contained keratins typical of fetal epidermis at 20 weeks gestation. Presence of filaggrin is variable at this age and depends on the presence of keratinized cells of hair canals. No keratin abnormalities in the fetus at risk for lamellar ichthyosis were detected, however, in one presumably normal biopsy, an abnormally low proportion of the 67 kd keratin and the presence of follicular keratins were evident. These results demonstrate that biochemical analysis of fetal biopsies is possible, thus increasing the diagnostic potential of the fetal biopsy procedure for disorders in which a known protein or antigen is altered in utero.
Justification of maternal serum alphafetoprotein screening in a population with low incidence of neural tube defects
Authors: Ghosh A. , Tang M. H. Y. , Nie D. Taig. , Ma H. K.
Published: March 2007

A prospective study of maternal serum alphafetoprotein (α‐FP) screening of 9838 women in an area with low prevalence of neural tube defects and predominance of anencephalics revealed that an intervention point of single serum α‐FP level above 2·8 times the median was appropriate for this population. Ninety per cent of anencephalics and all fetuses with anterior abdominal wall defects were detected. There was no spina bifida among the population screened. Two per cent of the population screened had serum α‐FP level above this cut‐off level. Thirty‐two per cent of twin pregnancies, 7 per cent of small‐for‐gestational age infants and 9 per cent of pregnancies which ended in either abortion or perinatal death in the population screened also had one serum α‐FP level above this intervention point. The false positive rate was 66 per cent. This false positive rate was only reduced to 63 per cent if instead of one, two serum α‐FP level above this intervention point was considered abnormal. Using this strategy there was no significant reduction in the detection rate of fetal anomalies and other pregnancy complications.

Because of the predominance of anencephalics in this population the diagnosis of fetal anomaly in women with abnormal serum a‐FP level was made by ultrasound examination alone. The reason amniocentesis was not performed in these patients was to avoid unnecessary loss of normal pregnancies which may result from this procedure.
First‐trimester prenatal diagnosis of severe alpha‐thalassemia
Authors: Liming Wang , Junwu Zhang , Guanyun Wu , Shenwu Wang , Yu Fan , Youwen Huang , Letian Zhao , Rongxin Wang , Jidong Su , Nijia Zhang , Guifang Long , Peng Li Qi, Zou , Rong Liang , Xu Liang
Published: March 2007

By means of chorion biopsy together with restriction endonuclease analysis of fetal DNA, first trimester diagnoses were successfully made in 33 fetuses at risk for Bart's hydrops fetalis. Seven pregnancies with Hb H or hydrops fetalis were therapeutically terminated before 4 months of gestation. Of the 26 pregnancies intended to continue, 18 have come to term with normal deliveries; one with threatened abortion was terminated at the end of the first trimester and, seven are progresssing normally.
Prenatal treatment of fetal hydrops associated with the hypertelorism‐dysphagia syndrome (opitz‐g syndrome)
Authors: Patton M. A. , Baraitser M. , Nickolaides K. , Rodeck C. H. , Gamsu H.
Published: March 2007

Non‐immunological fetal hydrops diagnosed prenatally presents a difficult diagnostic and therapeutic problem. In the case presented, fetal hydrops was recognized at 19 weeks gestation and no specific cause was found prenatally in spite of extensive investigations. The fetal hydrops was treated in utero by thoracocentesis and an intravenous infusion of albumin carried out at fetoscopy. After birth the infant was recognized to have the hypertelorismdysphagia syndrome (or Opitz‐G syndrome, McK no. 30710). This autosomal dominant syndrome consists of hypertelorism, laryngeal abnormalities, swallowing difficulties, hyprospadias and an imperforate anus. Fetal hydrops has been reported on one previous occasion in this syndrome. The intrauterine treatment given in this case may have been successful in reducing the neonatal complications of the Opitz‐G syndrome.
Cultured amniotic fluid cells for prenatal diagnosis of lysosomal storage disorders: A methodological study
Authors: Arnon Judith , Ornoy Asher , Bach Gideon
Published: March 2007

The influence of culture conditions on the ultrastructure and enzyme activities of amniotic fluid cells are reported. Morphological changes were determined as a function of the number of lysosomal‐like inclusion bodies per cell, and these results correlated to the activity of Thiexosaminidase, a‐mannosidase, β‐glucuronidase, arylsulphatase C and 5′ nucleotidase. The parameters examined were pH of the culture media, type of media, increasing cell passage and day of harvest.

Our results indicate that enzyme activities are less sensitive to changes in culture conditions as compared to ultrastructural changes. We therefore recommend that in order to obtain reliable ultrastructural results for the diagnosis of storage disorders, cultures should be grown in MEM as the culture medium, the pH of the medium carefully monitored to remain below pH 7·4, examining the cultures no later than the eighth cell passage and no later than the 10th day after subculture.
Rare chromosome 20 variants encountered during prenatal diagnosis
Authors: Petersen Michael B.
Published: March 2007

A case with an uncommon heteromorphism in the centromeric region of chromosome 20, var (20) (cen, CBG 50), and a family with a pericentric inversion of chromosome 20, inv (20) (p11.23q11.21), are reported, both detected in amniotic fluid cell cultures. It appears that small pericentric inversions of chromosome 20 have a low risk of recombination.
Admixture of maternal metaphases in first trimester direct chromosome preparations?
Authors: Jensen P. K. A. , Hertz J. M. , Therkelsen A. J.
Published: March 2007

The autoradiographic labelling of different cell types in chorionic villi and decidual tissue was investigated after [3H]‐thymidine incorporation in vitro. Although the extent of labelling was found to be lower in decidual than in villus tissue the possibility that direct chromosome preparations may contain maternal metaphases should be considered. The need for careful selection of villi for direct cytogenetic analysis was stressed.
Prenatal diagnosis of infantile GM 2 gangliosidosis type II (sandhoff disease) by detection of N‐acetylglucosaminyl‐oligosaccharides in amniotic fluid with high‐performance liquid chromatography
Authors: Warner Thomas G. , Wilson Turner M. , Toone Jennifer R. , Applegarth Derek
Published: March 2007

Prenatal diagnosis of Sandhoff disease (infantile onset) at 16 weeks gestation has been made by detection and analysis of N‐acetylglucosaminyl‐oligosaccharides in amniotic fluid using high performance liquid chromatography. The elution profile for the branched chain oli‐gosaccharides was identical with that obtained with neonatal and infantile Sandhoff urine. The concentration of the oligosaccharides in the fluid was 1/100th that of urine but when calculated relative to creatinine the levels were similar. No oligosaccharides were detected in normal control amniotic fluids (10 patients) at a similar gestational age. Based on the levels of the amniotic fluid oligosaccharides and the sensitivity limits of the assay, prenatal diagnosis of patients with the juvenile onset form of the disease may also be possible with this technique.
A pipette method for rapid karyotyping in prenatal diagnosis
Authors: Claussen Uwe , Klein Renate , Schmidt Marianne
Published: March 2007

The 'pipette method' is introduced as a method of prenatal diagnosis which is in competition with the 'in situ' and the 'trypsinization' technique. It is sufficiently standardized for routine diagnosis and the banding techniques currently used in prenatal diagnosis (G, Q, C‐banding and NOR) have been adapted for it.

In 180 cases from 27 different centres, the 'pipette method' was employed for chromosomal harvesting in order to save time. An average of 6·6 days was taken to achieve a result. There was a pathological karyotype in 28 cases (16·1 per cent) and this high proportion can be related to cases where ultrasound scan has led to a diagnosis of 'suspected chromosomal abnormality'. This technique is also of use in advanced stages of pregnancy. The early recognition of the fetal karyotype can contribute to the future management of the pregnancy.

The 'pipette method' can also be used in chromosomal harvesting of tumour cells and fibroblast cultures.
S‐100 protein and neuron‐specific enolase in amniotic fluid as markers of abdominal wall and neural tube defects in the fetus
Authors: Annerén G. , Esscher T. , Larsson L. , Olsen L. , Påhlman S.
Published: March 2007

The aim of this study was to determine whether there is increased leakage of neuron‐specific enolase (NSE) and S‐100 protein into amniotic fluid in pregnancies with neural tube defects, since both these proteins are produced by neural tissue, and to compare the value of these substances for detecting such defects with that of the more conventional techniques of alpha‐fetoprotein (AFP) and acetylcholinesterase (AChE) gel electrophoresis.

Amniotic samples from 25 mid‐pregnancies (15–17 weeks' gestation) with neural tube defects (14 with open spina bifida and 11 with anencephaly) and from seven mid‐pregnancies with abdominal wall defects were compared with a control material consisting of 80 amniotic fluid samples from 80 consecutive mid‐pregnancy amniocenteses, with normal karyotypes and AFP concentrations. All of the above cases of abnormalities were primarily detected through increased AFP levels in the amniotic fluid. Amniotic fluid samples from 13 pregnancies with fetuses with autosomal chromosomal abnormalities and seven amniotic fluid samples contaminated with blood were also included in the investigation.

It is concluded from the results that the conventional AFP assay combined with AChE gel electrophoresis is the best method for screening amniotic fluid for neural tube defects and defects of the abdominal wall. Neither NSE nor S‐100 assay alone proved to be superior for the detection of these cases in mid‐trimester amniotic fluid. The S‐100 assay, however, could give additional information in cases where AChE gel electrophoresis is not decisive; for example, in samples contaminated with blood.
Intrauterine hypercalcaemia and non‐immune hydrops fetalis— relationship to the Williams syndrome
Authors: Westgren M. , Eastham W. N. , Ghandourah S. , Woodhouse N.
Published: March 2007

We describe a 28‐week‐old fetus with severe non‐immune hydrpps. Intrauterine cord blood sampling revealed hypercalcaemia of 3–4mmol/l (n = 2·6±0·1). Subsequently, a postmortem examination revealed supravalvular aortic and pulmonary artery stenosis together with extensive arterial calcification. The maternal calcium, 25‐hydroxyvitamin D3, 1,25‐dihydroxyvitamin D3, and parathyroid hormone levels were normal at delivery.

This is the first time that hypercalcaemia has been diagnosed in vitro. We speculate on the fact that the disorder resulted as a consequence of abnormal vitamin D metabolism in the fetoplacental unit, and that it might be related to the Williams syndrome.
First trimester chorionic villus sampling versus mid‐trimester genetic amniocentesis‐preliminary results of a controlled prospective trial
Authors: Crane James P. , Beaver Heidi A. , Cheung Sau Wai
Published: March 2007

This controlled prospective study assesses the relative risks of first trimester chorionic villus sampling (CVS) versus mid‐trimester gentic amniocentesis (GA). CVS subjects and amnio‐centesis controls were comparable with regard to several confounding variables which might influence the risk of pregnancy loss including maternal age, smoking, alcohol consumption, gestational age at study entry, and history of vaginal bleeding or poor prior reproductive outcome. The most common indication for prenatal diagnosis was advanced maternal age (n = 511). In this subgroup, spontaneous abortion (<24 weeks) occurred in 2·9 per cent of CVS subjects versus 4−3 per cent of amniocentesis controls. The sum of spontaneous and therapeutic abortions (<24 weeks) was identical (5·3 per cent) in both groups. Therefore, intervention in the CVS group (i.e., therapeutic abortion for cytogenetic abnormalities) did not influence the observed risk of pregnancy loss. Overall perinatal mortality rates were also similar in both groups. No significant differences were identified for a number of pregnancy outcome parameters including 5 min Apgar score, birth weight, body length, head circumference, gestational age at delivery, preterm delivery, fetal growth retardation, congenital malformations, and neonatal complications. Preliminary results of this controlled prospective study suggest that chorionic villus sampling carries a low and acceptable risk.
In vitro characteristics of human fetal cells obtained from chorionic villus sampling and amniocentesis
Authors: Chang Hsiao‐Chen , Jones Oliver W.
Published: March 2007

In vitro characteristics of human fetal cells have been investigated after chorionic villus sampling at the first trimester and amniocentesis at the second trimester of pregnancy. Light microscopy revealed heterogeneous morphology of cell types in both the chorionic villus culture and the amniotic fluid cultures. Based on the experiments performed, chorionic villus cells are more sensitive to pronase, trypsin, and versene during subculture and have a higher DNA content per single cell and release more [125I]‐Beta‐human chorionic gonadotropin into culture medium than those found in amniotic fluid cells. The practical applications of this study are discussed.
The oxidation of octanoic acid by cultured amniotic fluid cells: The effect of cell type and passage number
Authors: Allison F. , Barnes I. C. S. , Bennett M. J.
Published: March 2007

We have measured the rate of oxidation of [1−14C]octanoate in cultured amniotic fluid (AF) cells at various passages and in AF cell lines with different clonal morphology. It is possible that both the passage number and the cell type may influence the outcome of prenatal diagnosis of fatty acid oxidation defects using this technique. We found that there was no significant difference between the three major AF cell types (epithelial, large epithelial, and fibroblast) when analysed at identical passage number but there was a significant reduction in octanoate oxidation in all cell types with increasing passage. For reliable prenatal diagnosis, cell lines of similar low passage number should be used.
Problems in prenatal diagnosis of β‐thalassaemia by fetal blood analysis: β‐chain variant comigrating with gamma chains
Authors: Rosatelli C. , Schettini F. , Monni G. , Tuveri T. , Scalas M. T. , Di Tucci A. , Leoni G. B. , Cao A.
Published: March 2007

This report describes a couple at risk for β thalassaemia in which one spouse was heterozygous for classical high Hb A2 β‐thalassaemia while the other had the compound heterozygous state for β+‐thalassaemia and a β‐chain variant. This variant comigrates on carboxymethyl‐cellulose columns (CMC) with γ‐chains, indicating that globin separation on CMC columns could not have been used for fetal diagnosis. The β‐chain variant migrates separately from the other globin chains on HPLC and the respective abnormal haemoglobin can be separated by isoelectrofocusing. Oligonucleotide hybridization showed that both parents were carriers of the β+ IVS‐1, nt 6 mutation. Prenatal diagnosis was successfully accomplished by oligo‐nucleotide analysis on trophoblast DNA. This case indicates that an Antenatal Service should have alternative methods to CMC columns so as to carry out prenatal diagnosis of β‐thalassaemia in uncommon cases.
Maternal cell contamination in chorionic villus samples assessed by direct preparations and three different culture methods
Authors: Roberts E. , Duckett D. P. , Lang G. D.
Published: March 2007

Presumptive maternal cell contamination (MCC) was monitored in identified male cases during cytogenetic comparison of direct techniques and three different culture regimes from 140 thoroughly dissected chorionic villus samples. Of the 66 identified male cases, 11(16·7 per cent) showed MCC, the mean number of cells examined per case being 8·2 (direct) and 14·5 (cultures); in the direct preparations only one of a total of 457 cells examined was female, while preparations from cultures revealed MCC in 11 cases. Four of these had MCC in more than one culture regime and four had only a single female cell. The results showed that (1) dependence on the culture system alone would have given a diagnosis based on maternal cells in one (1·5 per cent) male case, thus underlining the danger of this approach (a similar undetected rate of misdiagnosis being expected in the female cases) and (2) MCC was significantly lower in cultures grown in Chang medium as compared with the other two regimes, McCoy's 5A + 15 per cent fetal calf serum and 1 per cent Ultroser G, and McCoy's 5A + 25 per cent fetal calf serum, the latter expressing the highest level of MCC.
Cardiac defects in chromosomally abnormal human embryos of 10–14 weeks' gestation
Authors: Coerdt Wiltrud , Rehder Helga , Gebauer Hans‐Jürgen , Holzgreve Wolfgang , Klink Franz , Miny Peter , Schulze Bernt
Published: March 2007

Cardiac defects were studied in five chromosomally abnormal embryos of 10–14 weeks' gestation by free‐hand microdissection of hearts measuring 2·5–6 mm in diameter. The type of cardiac malformation alone or in association with other anomalies helped to confirm the chromosome diagnosis established prenatally by chorionic villus sampling or after spontaneous abortion. It was suggestive of a chromosomal disorder in one case in which cytogenetic investigation had failed.
Maternal sex chromosome mosaicism diagnosed by amniocentesis and percutaneous umbilical cord sampling
Authors: Hunter A. G. W. , D'Alton M. , Wey B. , Wang H. S. , Thompson D. W.
Published: March 2007

We present a remarkable chain of events in which percutaneous umbilical cord sampling was performed in an attempt to clarify a situation of possible fetal sex chromosome mosaicism in an amniotic fluid culture and led to the discovery that the mother herself had a 45,X/46,XX/ 47.XXX chromosome constitution. This may have simply represented the chance concurrence of pseudo‐mosaicism in the amniotic fluid culture of a woman with an abnormal sex chromosome constitution, but it is also possible that the 45,X colony was maternal in origin. Although clearly a most unusual circumstance, the possibility should be kept in mind when termination of a pregnancy is being considered because of apparent mosaicism in a prenatal diagnostic study.
A routine method for storing lymphocytes for repeated isolation of DNA
Authors: Jørgensen Bjarne R. , Therkelsen A. J.
Published: March 2007

A protocol for easy storage and later expansion of lymphocyte populations is given. Compared with methods using transformed cell lines, the method has a number of advantages for repeated production of cells for the isolation of DNA in amounts sufficient for use in diagnostic DNA technology.
Severe bilateral renal disease: Correlation of antenatal and autopsy findings
Authors: Murphy Jerome L. , Mendoza Stanley A. , Griswold William R. , Reznik Vivian M.
Published: March 2007

We report 20 infants with severe bilateral renal disease examined by prenatal ultrasound and by autopsy. In 17, the prenatal and pathologic diagnoses correlated well. Although the prenatal and autopsy findings differed in the three remaining cases, the autopsy confirmed the presence of severe bilateral renal abnormalities. All 20 pregnancies were complicated by oligohydramnios, which was severe in 60 per cent. Most of these fetuses had malformation of other organ systems. This series supports the utility of prenatal ultrasound examinations, but emphasizes the need for postnatal evaluation of congenital renal disease including pathologic examination of tissue when possible for correct classification and genetic counselling.
Prenatal diagnosis of Schwartz–Jampel syndrome with early manifestation
Authors: Hunziker Urs A. , Savoldelli Guido , Boltshauser Eugen , Giedion Andres , Schinzel Albert
Published: March 2007

A mother who had given birth to a child with Schwartz–Jampel syndrome (SJS) with neonatal manifestations (myotonia, congenital contractures, bowing of femora and tibiae) underwent ultrasonic fetal examination during the 17th and 19th week of her second pregnancy. Moderately decreased fetal motor activity and constant flexion of the fingers were observed at both examinations. In addition, there was mild bowing and shortening of the femora. At birth, the child presented with the characteristic pattern of SJS similar to her older brother. Prenatal ultrasonic diagnosis of Schwartz–Jampel syndrome is possible, at least for the form with neonatal onset of myotonia and contractures.
False‐negative amniotic fluid acetylcholinesterase in a case of meningo‐encephalocele
Authors: Boogert A. , Aarnoudse J. G. , de Bruijn H. W. A. , Gouw A.
Published: March 2007

We describe a patient with a significantly elevated serum alphafetoprotein (AFP) concentration at 17 weeks of gestation, who showed only a marginally increased amniotic fluid AFP and lacked the second rapidly migrating band of acetylcholinesterase electrophoresis. Ultrasound examination revealed an encephalocele and ventriculomegaly. Autopsy showed that the encephalocele was not covered by skin.
First‐trimester prenatal diagnosis of homozygous (14;21) translocation in a fetus with 44 chromosomes
Authors: Dallapiccola B. , Ferranti G. , Altissimi D. , Colloridi F. , Paesano R.
Published: March 2007

A (14;21) homozygous Robertsonian translocation was detected by first‐trimester prenatal diagnosis. The related parents were heterozygous for the same translocation. At birth the baby was physically normal and had a normal psychomotor development. Together with a few previous observations in living homozygotes for (13;14) translocations, this case corroborates the idea that these subjects with 44 chromosomes are healthy without dysmorphic features.
The European collaborative study on mosaicism in chorionic villus sampling: Data from 1986 to 1987
Authors: Vejerslev Lars O. , Mikkelsen Margareta
Published: March 2007

Data on a total of 11 855 diagnostic chorionic villus samples obtained in the years 1986 and 1987 were compiled from a questionnaire filled in by 36 European cytogenetic centres. Mosaicism was reported in 141 cases. The cytogenetic findings were followed by induced abortion in 24 cases. Spontaneous abortion was observed in nine mosaic pregnancies, a rate not significantly different from that observed for CVS in total. Mosaicism was found in 1.2 per cent of analyses by direct analysis/short‐term culture, in contrast to the 0.6 per cent found after long‐term culture. Evidence for fetal non‐mosaicism was found in 99 of the 141 cases. The finding of mosaicism in first‐trimester CVS should always elicit further analyses, preferably after amniocentesis, to substantiate the suspected fetal chromosome aberration.
Maternal serum alpha‐fetoprotein and fetal triploidy
Authors: Pircon Richard A. , Towers Craig V. , Porto Manuel , Gocke Stephen E. , Garite Thomas J.
Published: March 2007

Fetal triploidy is commonly found in early pregnancy. The majority of these pregnancies spontaneously abort in the first trimester. Occasionally, the pregnancy progresses to the second and third trimesters. We reviewed the maternal serum alpha‐fetoprotein (MSAFP), amniotic fluid alpha‐fetoprotein (AFP), amniotic fluid acetylcholinesterase (ACHE), fetal pathology, and placental pathology in sex second‐trimester pregnancies complicated by fetal triploidy. Four of these patients had MSAFP values greater than 7.5 multiples of the median (MoM). Five of six pregnancies had MSAFP values greater than 2.25 MoM. All five of these patients had a partial mole. Four patients had amniotic fluid AFP values greater than 2.0 MoM. Two fetuses had associated neural tube defects. These were the only patients with positive amniotic fluid ACHE. None of the other patients had fetuses with anomalies that are known to be associated with an elevated MSAFP. The elevated MSAFP appeared to be related to the presence of a partial mole. Two of the five cases with an MSAFP greater than 2.25 MoM did not have sonographic evidence of a significant anomaly. Therefore, karyotyping can be of benefit in evaluating patients with elevated MSAFP.
Harlequin fetus and micromelia
Authors: Charles A. , Moulinasse R. , Versailles L.
Published: March 2007

A fetus was born prematurely after a 34‐week pregnancy whose evolution was marked by the ultrasonic finding at 23 weeks of a considerable shortening of the long bones. At birth, the newborn infant bore the appearance of a harlequin fetus. There was no dwarfism, but the micromelia discovered in utero was confirmed both clinically and radiologically. Such global micromelia associated with this kind of pathology has never been described, not to mention witnessed, in utero and may be part of the fetal akinesia sequence phenotype.
Carrier detection and prenatal diagnosis in Norrie disease
Authors: Curtis Diana , Blank C. E. , Parsons M. A. , Hughes Howard N.
Published: March 2007

We report the use of DNA probes to determine carrier status in three young women from a large kindred with Norrie disease. One of the women requested prenatal diagnosis during pregnancy. In this pedigree, Norrie disease was not characterized by a deletion at DXS7.