bluuebunny/crossref_metadata_2025 huggingface dataset:
Early prenatal diagnosis of cartilage‐hair hypoplasia (CHH) with polymorphic DNA markers
Authors: Sulisalo Tuija , Sillence David , Wilson Meredith , Ryynänen Markku , Kaitila Ilkka
Published: March 2007

Cartilage‐hair hypoplasia (CHH) is an autosomal recessive disorder resulting in short stature and hypoplasia of hair. Associated features include impaired T‐cell‐mediated immunity, deficient erythropoiesis, gastrointestinal dysfunction, and an increased risk of malignancies. As the condition may, in some cases, be severe or even fatal during childhood, families with a previous history of CHH may wish to have prenatal diagnosis. We have previously assigned the gene for CHH to the proximal 9p by linkage analysis using several polymorphic DNA markers. Here we report the prenatal testing for CHH in three Finnish and one Australian family using three DNA markers closely linked to the CHH gene. In three cases a fetus unaffected with CHH was predicted at the probability level of more than 94 per cent. In one case, an affected fetus was predicted. The results were in concordance with ultrasonography performed for all fetuses. The three children born to date were unaffected as predicted. The DNA marker‐based analysis thus provides a useful method for early prenatal testing for CHH.
Fetal erythroblasts from maternal blood identified with 2,3‐bisphosphoglycerate (BPG) and in situ hybridization (ISH) using Y‐specific probes
Authors: Von Koskull Harriet , Gahmberg Nina
Published: March 2007

Different types of fetal nucleated cells can be found in maternal blood, providing the possibility of non‐invasive prenatal diagnosis. For this purpose, we have studied fetal erythroblasts. We discovered that haemoglobin‐containing cells treated with 2,3‐bisphosphoglycerate (BPG) can be visualized by a peroxidase reaction, which at the same time visualizes an in situ hybridization (ISH) signal, specific for the X, Y or 21 chromosome. In order to prove that the BPG‐positive cells were erythroid, an anti‐glycophorin A (GPA) antiserum combined with a staphylococcal rosette technique was used. To enrich for erythroblasts, leukocytes were depleted from maternal blood by treatment with anti‐CD45 monoclonal antibody and passage over an anti‐mouse IgG‐coated glass bead column. To evaluate the potential of the method for clinical use, we studied maternal blood samples from 18 women referred to us for prenatal diagnosis between 6 and 19 weeks of gestation. Erythroblasts were found in 13 out of 14 normal pregnancies. Erythroblasts with a Y‐signal were found as early as 9 weeks of gestation, but at 6 weeks the Y‐signal was seen in BPG‐negative cells only. These cells showed an epithelioid morphology indicating that they were cytotrophoblasts. The BPG‐ISH method provides a simple technique for identifying erythroblasts and simultaneously visualizing a desired probe.
The development of the fetal eye: In utero ultrasonographic measurements of the vitreous and lens
Authors: Achiron R. , Gottlieb Z. , Yaron Y. , Gabbay M. , Gabbay U. , Lipitz S. , Mashiach S.
Published: March 2007

Our objective was to establish nomograms for fetal eye measurements from 12 weeks' gestation by using transvaginal and transabdominal high‐resolution ultrasound techniques. A prospective cross‐sectional study was performed on 450 normal singleton pregnancies between 12 and 37 weeks' gestation. Vitreous and lens circumferences were measured by transvaginal ultrasonography until 17 weeks, and by abdominal ultrasound between 18 and 37 weeks' gestation. Regression analyses were used to create nomograms, and several transformations were done to obtain linearity. Eye measurements of 12 fetuses at risk for ocular disturbances were plotted on the constructed nomograms. Linear relationships were fitted between vitreous (r2=0.79) and lens (r2=0.88) circumferences and gestational age. In addition, there was a significant correlation between these measurements and the biparietal diameter. Data of the fetuses at risk showed that disturbances in ocular growth were associated mainly with abnormal cerebral development. These normative data may be helpful in the prenatal diagnosis of suspected congenital syndromes that include, among their manifestations, ocular growth disturbances such as microphthalmos and anophthalmos.
Collagen biosynthesis in cell culture from chorionic villi
Authors: Chamson A. , Bertheas M. F. , Frey J.
Published: March 2007

After chorionic villus biopsy of human placenta, cell cultures were propagated with Ham's F10 medium or Eagle's minimum essential medium (MEM). It was possible to study the morphology of the cells by transmission electron microscopy (TEM) after a special culture of the cells in a collagen gel. The cells embedded in a collagen gel were able to contract the gel and to organize collagen fibres, as fibroblast cultures do. TEM showed vacuolization and well‐developed cisternae of the endoplasmic reticulum, especially in the case of MEM culture. The aim was to determine whether cells cultivated from early placenta were able to synthesize enough collagen for a metabolic study. A high level of collagen biosynthesis could be quantified. Types I and III collagen can be determined which is useful for studying the abnormalities of collagen synthesis in suspected cases of osteogenesis imperfecta or Ehlers–Danlos type IV syndrome. The hydroxylation of lysine can also be studied with respect to Ehlers–Danlos type VI syndrome. Moreover, these cells, in contrast to fibroblast cultures, made it possible to study the biosynthesis of type IV collagen.
Prenatal diagnosis of Freeman–Sheldon syndrome (whistling face)
Authors: Robbins‐Furman P. , Hecht J. T. , Rocklin M. , Maklad N. , Greenhaw G. , Wilkins I.
Published: March 2007

The diagnosis of Freeman–Sheldon syndrome was made by ultrasonographic evaluation of a 20‐week fetus with a positive family history. The ultrasonographic features were abnormalities of the extremities and mouth.
Early prenatal diagnosis of an infratentorial arachnoid cyst: Association with an unbalanced translocation
Authors: Hogge W. Allen , Schnatterly Patricia , Ferguson James E.
Published: March 2007

Arachnoid cysts are an uncommon central nervous system malformation, representing only 1 per cent of all intracranial masses. We report the second‐trimester prenatal diagnosis of a posterior fossa arachnoid cyst, associated with an unbalanced X;9 translocation.
Digeorge syndrome with total monosomy 22 diagnosed prenatally
Authors: Merino A. , De Perdigo A. , Nomballais F. , Yyinec M. , Lopes P.
Published: March 2007

A case of monosomy 22 diagnosed prenatally is reported. During pregnancy, ultrasonic observations already revealed several cardiac malformations of the fetus in the 25th week. Following counselling, the pregnancy was terminated. Fetal autopsy revealed several abnormalities associated with DiGeorge syndrome.
Prenatal diagnosis of trisomy 21 using interphase fluorescence in situ hybridization of post‐replicated cells with site‐specific cosmid and cosmid contig probes
Authors: Soloviev Ilia V. , Yurov Yuri B. , Vorsanova Svetlana G. , Fayet Florance , Roizes Gerard , Malet Paul
Published: March 2007

Interphase fluorescence in situ hybridization (FISH) with chromosome 21‐specific cosmid clones was used to identify trisomy 21 in cultured and uncultured amniotic cells. Two novel site‐specific cosmid clones (regions 21q22 and 21qtel) were compared with a cosmid contig (Zheng et al., 1992). Correct identification of chromosome 21 copy number was made in 65–75 per cent of trisomic cells and in 70–75 per cent of normal disomic cells by using all the tested probes. However, the chromosome 21‐specific telomeric probe (cos 17F8) showed the best results due to more intense and clearly visible hybridization. Utilization of a directly fluorophorated telomeric probe using Cy3‐dCTP and FluorX‐dCTP allows accurate detection of chromosome 21 in a fast ‘one‐step’ FISH procedure on uncultured interphase nuclei. In addition, we compared the efficacy of FISH analysis for the total population of interphase cells and cells in the post‐replication (late S, G2) periods of the cell cycle. Selective scoring of cells in the post‐replicative period (showing a pair of hybridization signals on each chromatid of the replicated interphase chromosome) increased the number of informative nuclei by up to 95–97 per cent. This approach allows cells with overlapping chromosomes, artificial double hybridization signals on separate chromatids in interphase chromosomes, background hybridization, and polyploid cells to be analysed. Application of directly labelled telomeric cosmid probes and integral analysis of hybridized nuclei in the pre‐ and post‐replication periods of the cell cycle may help to further improve the prenatal detection of trisomy 21.
Detection of fetal HLA‐DQα sequences in maternal blood: A gender‐independent technique of fetal cell identification
Authors: Geifman‐Holtzman Ossie , Holtzman Eliezer J. , Vadnais Theresa J. , Phillips Vincent E. , Capeless Eleanor L. , Bianchi Diana W.
Published: March 2007

The objective of this study was to detect fetal HLA‐DQα gene sequences in maternal blood. HLA‐DQα genotypes of 70 pregnant women and their partners were determined for type A1. We specifically sought couples where the father, but not the mother, had genotype A1. In 12 women, maternal blood samples were flow‐sorted. Candidate fetal cells were isolated and amplified by using PCR primers specific for a paternal HLA‐DQα A1 allele. Fetal HLA‐DQα A1 genotype was predicted from sorted cells; amniocytes or cheek swabs were used for confirmation. Six of twelve sorted samples had amplification products indicating the presence of the HLA‐DQα A1 allele; 6/12 did not. Prediction of the fetal genotype was 100 per cent correct, as determined by subsequent amplification of amniocytes or cheek swabs. We conclude that paternally inherited uniquely fetal HLA‐DQα gene sequences can be identified in maternal blood. This system permits the identification of fetal cells independent of fetal gender, and has the potential for non‐invasive prenatal diagnosis of paternally inherited conditions.
Prenatal diagnosis of mosaic 4p – in a fetus with trisomy 21
Authors: Phelan Mary C. , Saul Robert A. , Gailey Thompson A. , Skinner Steven A.
Published: March 2007

Mosaicism for the Wolf‐Hirschhorn syndrome, del(4)(p16), is extremely rare and has not been reported in association with a numerical chromosome abnormality. We report the prenatal diagnosis of mosaic del(4)(p16) and non‐mosaic trisomy 21 in a 16‐week female fetus. The pregnancy ended in spontaneous abortion at 34 weeks secondary to fetal demise. The fetus had features of both 4p – and trisomy 21.
Fetal translocation between chromosomes 2, 18, and 21 resolved by fish
Authors: Delaroche Isabella , Sabani Margherita , Calabrese Giuseppe , Mingarelli Rita , Palka Giandomenico , Dallapiccola Bruno
Published: March 2007

An apparently balanced t(2q;21q) translocation was discovered in fetal blood and amniocytes of a 22‐week fetus, monitored because of ultrasonographic evidence of a heart disease. FISH (fluorescence in situ hybridization) analysis disclosed a complex translocation between chromosomes 2q, 18q, and 21q, which was inherited from the healthy mother. This observation corroborates the usefulness of molecular cytogenetic techniques in raising the quality of prenatal diagnosis and detecting subtle rearrangements not resolved by standard cytogenetics.
Detecting neural tube defects by amniocentesis between 11 and 15 weeks' gestation
Authors: Crandall B. F. , Chua C.
Published: March 2007

Forty‐two open neural tube defects (NTDs) were identified in our series of 7440 amniocenteses tested between 11 and 15 weeks of gestation. Using a cut‐off of ≥2.0 MOM, the detection rate for open NTDs was 95 per cent; 100 per cent each for anencephaly and spina bifida; and 78 per cent for encephalocele. Two encephaloceles had AFP levels less than 2.0 MOM and negative AChEs. Thirty‐four (81 per cent) of these NTDs were tested between 13 and 15 weeks and 8 (19 per cent) before 13 weeks. There were 0.6 per cent false positives by AFP (excluding serious abnormalities and fetal death) and 0.1 per cent after AChE. The likelihood of an open NTD after an elevated AFP (≥2.0 MOM) was 24 and 77 per cent for any serious abnormality. These results, when combined with an earlier study, indicate that amniotic fluid AFP appears to be as sensitive a test for open NTDs between 13 and 15 weeks as between 16 and 20 weeks. Additional experience is necessary to determine this before 13 weeks.
DNA‐based carrier detection and prenatal diagnosis of tyrosinase‐negative oculocutaneous albinism (OCA1A)
Authors: Falik‐Borenstein Tzipora C. , Holmes Stuart A. , Borochowitz Zvi , Levin Abi , Rosenmann A. , Spritz Richard A.
Published: March 2007

We describe molecular prenatal diagnosis and carrier detection of tyrosinase‐negative oculocutaneous albinism (OCA1A) in two families. In one family, we carried out DNA‐based prenatal diagnosis of OCA1A. In the other family, mutation analysis and carrier detection obviated the need for prenatal diagnosis. Molecular analysis is safer and probably more accurate than fetoscopy and fetal scalp biopsy, and should become the method of first choice for prenatal diagnosis of OCA1.
Prenatal diagnosis in a family with mitochondrial acetoacetyl‐coenzyme a thiolase deficiency with the use of the polymerase chain reaction followed by the heteroduplex detection method
Authors: Fukao Toshiyuki , Wakazono Akihiro , Song Xiang‐Qian , Yamaguchi Seiji , Zacharias Rebecca , Donlan Michael A. , Orii Tadao
Published: March 2007

Mitochondrial acetoacetyl‐coenzyme A (CoA) thiolase deficiency is an organic aciduria which affects isoleucine and ketone body catabolism. GK16 (the index patient) was affected with this disorder and previous studies had revealed that GK16 was a compound heterozygote with IVS8(+1) gt to tt and A301P mutations. In a subsequent pregnancy, prenatal diagnosis was performed and the fetus's amniocytes were analysed by the polymerase chain reaction (PCR) followed by the heteroduplex detection method on a Mutation Detection Enhancement gel. The fetus was identified as a carrier of the IVS8(+1) mutation. We confirmed the diagnosis by immunoblot analysis of extracted amniocytes and gene analysis with blood filter paper after delivery. This is the first report of prenatal diagnosis of this disorder at the gene level.
Sonographically determined anomalies and outcome in 170 chromosomally abnormal fetuses
Authors: Wladimiroff Juriy W. , Bhaggoe Wydia R. , Kristelijn Miranda , Cohen‐Overbeek Titia E. , Den Hollander Nicolette S. , Brandenburg Helen , Los Frans J.
Published: March 2007

Structural pathology and outcome were studied in 170 chromosomally abnormal fetuses. Numerical chromosomal abnormalities were established in 158 (93 per cent) cases, of which 110 (71 per cent) represented trisomies, 30 (18 per cent) Turner syndrome, and 18 (11 per cent) triploidy. Structural chromosomal abnormalities were diagnosed in 12 (7 per cent) cases. Gestational age at referral was significantly shorter for pregnancies with Turner syndrome than for the other chromosomal abnormalities. Referral before 20 weeks of gestation was mainly based on fetal structural pathology alone (92 per cent); after 20 weeks, patients were referred because of structural pathology combined with small for gestational age, oligohydramnios, or polyhydramnios. Referral as a result of suspected multiple organ pathology occurred in 73.5 per cent of pregnancies. An abnormal amniotic fluid volume was present in 59/170 (34.5 per cent) chromosomally affected pregnancies, i.e., oligohydramnios in 31 and polyhydramnios in 28 cases. Birth weight was below the tenth percentile in over half of the chromosomally abnormal fetuses, except for Turnersyndrome. Fetal outcome was poor, with a survival rate at 1 month of 30 per cent for trisomies which was mainly determined by trisomy 21 (14/18=77.5 per cent).
A misdiagnosis of X‐linked adrenoleucodystrophy in cultured chorionic villus cells by the measurement of very long chain fatty acids
Authors: Gray R. G. F. , Green A. , Cole T. , Davidson V. , Giles M. , Schutgens R. B. H. , Wanders R. J. A.
Published: March 2007

A case is reported of a male fetus at risk of X‐linked adrenoleucodystrophy who showed a normal cultured chorionic villus cell very long chain fatty acid (VLCFA) profile but at birth exhibited grossly abnormal plasma and cultured fibroblast VLCFAs. Maternal contamination or a sample mix‐up was excluded by chromosome analysis and analysis of polymorphic markers. This is the second report of a fetus affected with this disorder who showed normal cultured chorionic villus cell VLCFAs. It highlights the importance of a proper audit of all prenatal diagnoses to evaluate method reliability.
Short communication the natural history of fetal cytomegalovirus infection as assessed by serial ultrasound and fetal blood sampling: A case report
Authors: Watt‐Morse Margaret L. , Laifer Steven A. , Hill Lyndon M.
Published: March 2007

A patient in whom intrauterine fetal cytomegalovirus (CMV) infection was diagnosed at approximately 25 weeks' gestation is presented. The fetus was evaluated by serial fetal blood samplings and ultrasound examinations. The fetus manifested evidence of severe thrombocytopenia and hepatic inflammation, with recovery over a period of approximately 8 weeks. The initial sonographic findings of marked fetal ascites and cardiomegaly gradually resolved; ventriculomegaly developed during the third trimester. At delivery, the baby was morphologically normal with the exception of mild ventriculomegaly. Cord blood was negative for CMV IgM but urine was culture‐positive for CMV. At age 3, the child has a severe but stable unilateral hearing deficit and is otherwise developmentally normal. This case demonstrates the utility of serial ultrasound and fetal blood sampling in the prenatal diagnosis and management of fetal CMV infection.
Prenatal diagnosis of trisomy 9. Six cases and a review of the literature
Authors: Saura R. , Traore W. , Taine L. , Wen Z. Q. , Roux D. , Maugey‐Laulom B. , Ruffie M. , Vergnaud A. , Horovitz J.
Published: March 2007

Six prenatally diagnosed cases of trisomy 9 are reported and 22 previously reported cases are reviewed; the difficulty of genetic counselling for such cases and the variation in the percentage of trisomic cells in different tissues, thus making accurate diagnosis of trisomy 9 difficult, are emphasized. In addition to karyotyping results, ultrasound findings are important in achieving diagnoses. Finally, a course of action when prenatal trisomy 9 is detected is proposed.
A 10‐year survey, 1980–1990, of prenatally diagnosed small supernumerary marker chromosomes, identified by fish analysis. Outcome and follow‐up of 14 cases diagnosed in a series of 12 699 prenatal samples
Authors: Brøndum‐Nielsen K. , Mikkelsen M.
Published: March 2007

A cytogenetic survey and follow‐up studies were made of 14 cases with supernumerary marker chromosomes, identified among 12 699 prenatal samples, investigated at our institution over a 10‐year period from 1980 to 1990. FISH (fluorescence in situ hybridization) techniques were employed to identify the chromosomal origin of the marker chromosomes. Five cases were familial, all derived from acrocentric chromosomes, and all without apparent phenotypic effects in the children. Nine cases represented de novo aberrations. In two cases (one with a marker from chromosome 14 or 22, the other with a ring‐like marker derived from chromosome 17), the pregnancies continued and apparently normal babies were delivered at term, but the child with a marker derived from chromosome 17 showed slight psychomotor retardation at 2 years of age. All other pregnancies with de novo markers were terminated. In three cases, significant abnormalities were found at autopsy. One of these had an isochromosome 12p and the phenotype was consistent with Pallister‐Killian syndrome. In conclusion, marker chromosome identification, as well as clinical follow‐up, is essential for the purpose of improving genetic counselling.
Prenatal diagnosis of charcot‐marie‐tooth disease type 1a (CMT1A) using molecular genetic techniques
Authors: Navon R. , Timmerman V. , Löfgren A. , Liang P. , Nelis E. , Zeitune M. , Van Broeckhoven C.
Published: March 2007

Charcot‐Marie‐Tooth disease type 1A (CMT1A) is a frequent hereditary motor and sensory neuropathy of the peripheral nerves. In most cases, the disease is associated with a 1.5 Mb tandem duplication at 17p11.2. A 42‐year‐old pregnant woman requested prenatal diagnosis because of her age and since both her husband and two children were severely affected with CMT1. The CMT1A duplication was demonstrated in the father's, the two children's, and the fetus's DNA using different molecular genetic methods. Although cytogenetical analysis showed a normal female karyotype in the fetus, the parents decided to terminate the pregnancy because of the genetic risk associated with the CMT1A duplication.
The time of appearance and disappearance of fetal DNA from the maternal circulation
Authors: Thomas M. R. , Tutschek B. , Frost A. , Rodeck C. H. , Yazdani N. , Craft I. , Williamson R.
Published: March 2007

A single copy Y‐chromosome DNA sequence was amplified using the polymerase chain reaction (PCR) from the peripheral blood of 30 women who had achieved a pregnancy through an in vitro fertilization (IVF) programme. The time of conception was known precisely and was confirmed by serial ultrasound scans. Conceptions were dated as the number of weeks after fertilization plus 2, to give a time equivalent to the obstetric menstrual dating of the pregnancy (LMP). Y‐chromosome‐specific DNA was detected in all pregnancies with a male fetus (18/30). The earliest detection was at 4 weeks and 5 days, and the latest at 7 weeks and 1 day. Y‐chromosome‐specific sequences were no longer detected in any of the male pregnancies 8 weeks after delivery. No Y‐chromosome sequences were detected in any of the pregnancies where only female babies were delivered. This demonstrates that fetal DNA appears in the maternal circulation early in the first trimester, that it can be identified in all pregnancies tested by 7 weeks, that it continues to be present throughout pregnancy, and that it has been cleared from the maternal circulation 2 months after parturition. Early non‐invasive prenatal diagnosis for aneuploidies and inherited disorders will be possible in all pregnancies if fetal cells can be isolated free from maternal contamination (or identified accurately in the presence of maternal cells) without problems of contamination from previous pregnancies.
Genetic basis of lethal junctional epidermolysis bullosa in an affected fetus: Implications for prenatal diagnosis in one family
Authors: McGrath John A. , McMillan James R. , Dunnill M. Giles S. , Pulkkinen Leena , Christiano Angela M. , Rodeck Charles H. , Eady Robin A. J. , Uitto Jouni
Published: March 2007

Fetal skin biopsy at 20 weeks' gestation in a woman at risk for a child with the lethal skin‐blistering disorder junctional epidermolysis bullosa (Herlitz) confirmed an affected fetus. Genomic DNA from the aborted fetus was examined for mutations in laminin 5, a macromolecule involved in adhesion at the dermal‐epidermal junction, and a candidate protein in this condition. Polymerase chain reaction (PCR) amplification of exon 10 and parts of the flanking introns of the gene encoding the β3 chain of laminin 5 (LAMB3) and subsequent analysis by agarose gel electrophoresis showed a more slowly migrating band in the affected fetus compared with the normal control. Nucleotide sequencing of the abnormal PCR product revealed a homozygous 77 bp duplication within the exon, resulting in a premature termination codon 250 bp downstream from the 3′ end of the duplication. Maternal DNA was heterozygous for the mutant and wild‐type alleles. These findings illustrate the genetic basis of the skin disease in this case and also offer the prospects of a simple, rapid, and reliable first‐trimester DNA‐based prenatal, or even preimplantation, diagnostic test for future pregnancies in this family.
Prenatal ultrasound diagnosis of amelia
Authors: Rijhsinghani A. , Yankowitz J. , Mazursky Jon , Williamson R.
Published: March 2007

Amelia is a very rare form of limb reduction defect. The incidence of isolated amelia with or without other limb reductions is 0.4 per 100 000 births. We report a cluster of three cases diagnosed prenatally. One was isolated tri‐amelia and two were isolated tetra‐amelia.
Short‐rib polydactyly syndrome (SRPS) type III diagnosed during routine prenatal ultrasonographic screening. A case report
Authors: Meizner Israel , Barnhard Yoni
Published: March 2007

The prenatal diagnosis of skeletal dysplasias is often initiated by the finding of a shortened extremity during a routine sonographic examination. Second‐trimester diagnosis of these anomalies allows the couple to consider the option of terminating a pregnancy when a lethal anomaly is detected. A 21‐year‐old Bedouin woman underwent routine ultrasonographic screening at 20 weeks' gestation. Severe micromelia, a narrow thorax with shortened ribs, and postaxial polydactyly were detected. The patient delivered a male dwarf at 20 weeks' gestation following prostaglandin induction of labour for a diagnosis of short‐rib polydactyly syndrome type III. The prenatal ultrasonographic diagnosis of short‐rib polydactyly syndrome type III was made at 20 weeks' gestation, allowing termination of the pregnancy. A proper sonographic approach to skeletal dysplasias allows both early detection and differentiation between lethal and non‐lethal anomalies.
DNA‐based prenatal carrier detection for group a xeroderma pigmentosum in a chorionic villus sample
Authors: Matsumoto Naomichi , Saito Nakamichi , Harada Naoki , Tanaka Kiyoji , Niikawa Norio
Published: March 2007

DNA‐based prenatal carrier detection of group A xeroderma pigmentosum (XP‐A) is reported. Chorionic villus sampling was done at the tenth gestational week in a pregnant woman whose first child suffers from XP‐A. Genomic DNAs from the villi, proband, and parents were PCR (polymerase chain reaction)‐amplified using three sets of primers, because the PCR and a subsequent enzyme digestion with HphI, AlwNI, or MseI may detect the three most frequent mutations of the XP‐A complementing gene (XPAC) in Japanese XP‐A patients. The results showed that the proband is a homozygote and that the parents and fetus are heterozygotes for a base substitution at the 3′ acceptor site of intron 3 of XPAC, indicating that the fetus is a healthy carrier of XP‐A. This is the first case of prenatal carrier detection of the disorder.
Prenatal diagnosis of congenital diaphragmatic hernia: Timing of visceral herniation and outcome
Authors: Bronshtein Moshe , Lewit Nathan , Sujov Polo O. , Makhoul Imad R. , Blazer Shraga
Published: March 2007

Ultrasonographic prenatal diagnosis of congenital diaphragmatic hernia is well established, but the correlation of prenatal detection with clinical outcome remains unclear. We report our experience with 15 cases of prenatally diagnosed congenital diaphragmatic hernia. Seven fetuses were detected at 14–16 weeks' gestation; two with a normal sonographic study at 15 and 16 weeks' gestation showed visceral herniation at 21 and 23 weeks, respectively. In the remaining six cases, a diaphragmatic hernia was found at ultrasonography after 24 weeks' gestation, while previous sonographic studies had been normal. All seven fetuses in whom a diaphragmatic hernia was diagnosed before 16 weeks' gestation were aborted; four of them had severe malformations or karyotype abnormalities. The two neonates who were diagnosed at 21 and 23 weeks' gestation died after surgical repair. In contrast, all six infants whose visceral herniation was diagnosed after 24 weeks of gestation, and whose sonographic studies at 15–23 weeks had been normal, are alive and well after corrective surgery. The results of this series suggest that the timing of visceral herniation into the thoracic cavity is a major indicator of the prognosis of these fetuses and that herniation that occurs after 25 weeks of gestation carries a favourable clinical outcome. Normal sonographic studies during the first half of pregnancy do not exclude the subsequent development of congenital diaphragmatic hernia, raising questions about the advisability of repeat examinations at later stages of gestation.
Fetal ductus venosus flow velocity waveforms and maternal serum afp before and after first‐trimester transabdominal chorionic villus sampling
Authors: Brezinka Christoph , Hagenaars Adriana M. , Wladimiroff Juriy W. , Los Frans J.
Published: March 2007

Doppler flow velocity waveform recording in the fetal ductus venosus and umbilical artery as well as maternal blood sampling for serum alpha‐fetoprotein (MSAFP) was performed before and after transabdominal chorion villus sampling (TACVS) in 36 women of advanced maternal age (≥ 36 years). Gestational age ranged between 11 and 13 weeks. No chromosomal anomaly was detected. No statistically significant difference was observed in ductus venosus velocity parameters or in the umbilical artery pulsatility index (PI) before and after CVS in 35 women with a normal pregnancy outcome. One case resulted in fetal loss. Post‐CVS median MSAFP levels at 12 weeks (25 kIU/1) and 13 weeks (35 kIU/1) were significantly higher than pre‐CVS levels. In three cases, post‐CVS MSAFP levels were higher than 600 kIU/1, correlating with feto‐maternal transfusions of approximately 1.0–1.4 ml, i.e., of around 40 per cent of feto‐placental blood volume. One of these cases displayed absence of fetal peripheral blood flow velocities and fetal bradycardia following TACVS, resulting in fetal loss 1 week later. The remaining two cases had a normal pregnancy outcome, but showed a more than 50 per cent reduction in ductus venosus velocity after TACVS, whereas umbilical artery PI remained unchanged. However, similar velocity changes were associated with only small feto‐maternal transfusions. Umbilical artery PI values remained unchanged.
Risk‐based prenatal screening for trisomy 18 using alpha‐fetoprotein, unconjugated oestriol and human chorionic gonadotropin
Authors: Palomaki Glenn E. , Haddow James E. , Knight George J. , Wald Nicholas J. , Kennard Anne , Canick Jacob A. , Saller Devereux N. , Blitzer Miriam G. , Dickerman Lois H. , Fisher Rachel , Hansmann Dagmar , Hansmann Manfred , Luthy David A. , Summers Anne M. , Wyatt Philip
Published: March 2007

Nine centres collaborated to examine the feasibility of a screening method for trisomy 18 that was based on assigning individual risk, using a combination of maternal age and measurements of alpha‐fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotropin (hCG). Second‐trimester measurements of these analytes were obtained from 94 trisomy 18 pregnancies. In the 89 pregnancies without an associated open defect, the median levels for AFP, uE3, and hCG were 0.65, 0.43 and 0.36 multiples of the unaffected population median, respectively. The strongest individual predictor of risk for trisomy 18 was uE3, followed by hCG, AFP, and maternal age, in that order. Using a method of individual risk estimation that is based on the three markers and maternal age, 60 per cent of pregnancies associated with trisomy 18 would be detected at a risk cut‐off level of 1:100, with a false‐positive rate of about 0.2 per cent. One in nine pregnancies identified as being at increased risk for trisomy 18 would be expected to have an affected pregnancy. This risk‐based screening method is more efficient than an existing method that is based on fixed analyte cut‐off levels. Even though the birth prevalence of trisomy 18 is low, prenatal screening can be justified when performed in conjunction with Down syndrome screening and when a high proportion of women offered amniocentesis have an affected fetus.
The effect of thermal instability of intact human chorionic gonadotropin (ihcg) on the application of its free β‐subunit (free βhcg) as a serum marker in down syndrome screening
Authors: Sancken U. , Bahner D.
Published: March 2007

The kinetics of free βhCG concentrations were measured in 30 maternal whole blood samples from second‐trimester pregnancies during 72 h incubation at 3, 20, and 30°C. Dissociation of intact hCG (ihCG) was undetectable at 3°C and produced a more than 20 per cent increase of free βhCG at 20°C and a more than 100 per cent increase at 30°C. hCG dissociation at 30°C was not reduced by a protease inhibitor (sodium iodoacetate) and also occurred in purified hCG dissolved in a protease‐free incubation medium. These results were reproduced under conditions of sample transport by post at different environmental temperatures. In conclusion, reliable free βhCG assessment requires that the specimen be kept cool from vene puncture until assay or completely other transport strategies have to be considered. Evaluation of free βhCG as an effective marker in prenatal Down syndrome screening must be reconsidered from this aspect.
Prenatal ultrasonographic diagnosis of congenital megalourethra
Authors: Wu Meng‐Hsing , Wu Rong‐Chang , Kuo Pao‐Lin , Huang Ko‐En
Published: March 2007

Congenital megalourethra is a rare genital anomaly characterized by dilatation of the penile urethra without evidence of distal obstruction. Reports of the prenatal diagnosis of this condition in the literature are limited. We present a case of congenital megalourethra with obstructive uropathy from the posterior urethra diagnosed prenatally at 18 weeks of gestation. ‘Prune‐belly’‐like features, colonic malrotation, and imperforate anus were also found on autopsy.
A case of paternal uniparental disomy for chromosome 11
Authors: Webb A. , Beard J. , Wright C. , Robson S. , Wolstenholme J. , Goodship J.
Published: March 2007

We report a case of paternal uniparental disomy for chromosome 11 that presented as severe intrauterine growth retardation. Autopsy following intrauterine death also revealed aberrant intestinal rotation and hypospadias. Chromosome analysis of direct preparations from placental biopsy showed an abnormal 47,XY,+11 karyotype. Analysis of long‐term cultures from the placenta revealed 46,XY/47,XY,+11 mosaicism. Fluorescence in situ hybridization (FISH) studies on interphase nuclei confirmed trisomy 11 in multiple placental sites but detected only disomic cells in fetal skin. Investigation using microsatellite polymorphisms demonstrated paternal isodisomy at loci D11S909, D11S956, and D11S488, and paternal heterodisomy at locus D11S928.
Early prenatal diagnosis of ventricular diverticulum complicated by serous pericardial effusion
Authors: Carles D. , Maugey‐Laulom B. , Habboud H. , Alberti E. M. , Weichhold W. , Léger F.
Published: March 2007

An unusual case of apical diverticulum complicated by serous pericardial effusion and diagnosed ultrasonographically at 13 weeks of gestation is described. A therapeutic abortion was induced at 14 weeks and the complete post‐mortem examination did not show additional malformation. Cardiac diverticulum is a rare malformation that occurs as an isolated defect or as part of a complex midline thoraco‐abdominal defect. Only two prenatally diagnosed cases have been previously reported in the literature and none with associated hydropericardium.
Evaluation of routine prenatal diagnosis by a registry of congenital anomalies
Authors: Stoll C. , Dott B. , Alembik Y. , Roth M. P.
Published: March 2007

Prenatal diagnosis performed by ultrasound scan is now a routine part of prenatal care in many countries. How many fetal anomalies are actually detected by these procedures? We have used our registry of congenital malformations to answer this question. In a previous study (Prenat. Diagn., 12, 263–270, 1992), considering the period 1979–1988, we have shown that prenatal diagnosis was performed in 23.1 per cent of fetuses with a chromosomal aberration and in 20.1 per cent of fetuses with non‐chromosomal anomalies. In 1991 and 1992, the percentatge of termination for Down syndrome was 44.4 and 41.9 per cent, respectively. From 1989 to 1992, the detection rate and the specificity of prenatal diagnosis by ultrasonographic examination were improved. The detection rate for isolated malformations (fetuses with only one anomaly) and for multiple malformed children was 26.2 and 66.0 per cent, respectively. The detection rate of congenital anomalies by ultrasonography was variable for the different categories of malformation. A high detection rate was observed for anencephaly (100 per cent) and urinary tract malformation. A low detection rate was seen for cleft lip (17.5 per cent) and limb reduction defects (18.2 per cent).
Prenatal diagnostic testing for familial dysautonomia using linked genetic markers
Authors: Oddoux Carole , Reich Elsa , Axelrod Felicia , Blumenfeld Anat , Maayan Channa , Slaugenhaupt Susan , Gusella James , Ostrer Harry
Published: March 2007

Familial dysautonomia (FD), a recessively inherited disease, has been mapped to chromosome 9q31. Highly polymorphic dinucleotide repeat markers flanking the genetic locus and at the same genetic location have been identified. We describe the prenatal diagnosis of FD using linkage and linkage disequilibrium analyses with these markers. Twelve families were analysed for informativeness and of these, seven went on to have prenatal testing (a total of eight fetuses tested). All of these fetuses were predicted to be heterozygous unaffected (FD carriers). Seven fetuses have come to term and are normal. In the absence of a recombinant proband, a panel of three proximal and three distal markers is sufficient to provide informative flanking markers and an 87–96 per cent likelihood of a highly predictive test. In an additional family at 1:4 risk for FD, no DNA was available from the propositus. This family was analysed using linkage disequilibrium to the #18 allele of the tightly linked marker D9S58 in conjunction with linkage analysis using data from two unaffected children. Prenatal diagnosis in this family indicated an affected fetus.
Cross‐hybridization of the chromosome 13/21 alpha satellite DNA probe to chromosome 22 in the prenatal screening of common chromosomal aneuploidies by fish
Authors: Verlinsky Y. , Ginsberg N. , Chmura M. , Freidine M. , White M. , Strom C. , Kuliev A.
Published: March 2007

In a routine application of commercially available centromeric DNA probes for the prenatal screening of common trisomies involving the autosomes 13, 18, and 21, and sex chromosomes, four cases of discrepancy between fluorescence in situ hybridization (FISH) results and follow‐up cytogenetic analysis were observed from a total of 516 cases of amniocentesis. In three of these cases, the results were false negative, and in one false positive. In this case, amniocentesis was performed because of a positive triple test in a 34‐year‐old woman with previous infertility treatment. The alpha satellite DNA probe for chromosomes 13/21 revealed five signals in 50 per cent of uncultured amniocytes, while standard cytogenetic analysis showed a normal karyotype. FISH analysis on metaphase chromosomes demonstrated the location of the additional signal in the centromeric region of chromosome 22. This additional signal was also present in the centromeric region of chromosome 22 of the mother, providing evidence for a possible inherited polymorphism in chromosome 22 responsible for unspecific hybridization with the alpha satellite probe for chromosomes 13/21 in this case. The observed polymorphism in centromeric regions may contribute to unreliability of the use of the 13/21 alpha satellite probe for prenatal screening by FISH.
Identification of a case of maternal uniparental disomy of chromosome 10 associated with confined placental mosaicism
Authors: Jones Carrie , Booth Carol , Rita Debra , Jazmines Lydia , Spiro Rhonda , McCulloch Brian , McCaskill Christopher , Shaffer Lisa G.
Published: March 2007

We report a case of maternal uniparental disomy of chromosome 10 discovered after chorionic villus sampling (CVS). Direct preparations revealed mosaic trisomy 10, while cultured CVS cells, as well as amniotic fluid cells, showed only a normal 46,XY complement. DNA analysis using microsatellite markers showed both chromosomes 10 to have been inherited from the mother. The pregnancy was complicated by polyhydramnios. A phenotypically normal male infant of appropriate size was delivered by Caesarean section at 41 weeks' gestation. Since only the direct preparations showed trisomy 10, this case illustrates the importance of CVS direct preparations in the detection of pregnancies at risk of uniparental disomy (UPD). Although the increased frequency of confined placental mosaicism (CPM) diagnosed when direct preparations are performed has been viewed negatively, identification of both CPM and UPD may have biological and clinical significance for a pregnancy. Even though only a single case of maternal disomy 10 is reported here, the apparently normal phenotype provides evidence that there are no major imprinted loci on chromosome 10 that affect in utero growth and development. However, other potential effects such as mental retardation will require long‐term follow‐up of this as well as additional cases.
Non‐immunological hydrops fetalis and intrapericardial teratoma: Case report and review
Authors: Perez‐Aytes Antonio , Sanchis Nuria , Barbal Agnes , Artés Maria Jose , Domene Julio , Chirivella Melitina , Baamonde Andres
Published: March 2007

A large intrapericardial teratoma was found at necropsy in a 38−week stillborn fetus, in which prenatal diagnosis of hydrops fetalis and an ehogenic cardiac mass had been made. Clinical and pathological data are reported. In utero intrapericardial teratomata lead to different outcomes depending on whether fetal hydrops is associated. When generalized fetal hydrops is not present, the outcome is good, even in cases with large pericardial effusions. When generalized fetal hydrops occurs, it often results in a poor outcome. In our literature review, we have found eight perinatal deaths in nine similar cases reported.
Fetal ascites and oligohydramnios: Prenatal diagnosis of a sialic acid storage disease (index case)
Authors: Poulain P. , Odent S. , Maire I. , Milon J. , Proudhon J. F. , Jouan H. , Le Marec B.
Published: March 2007

In a 20‐year‐old primiparous patient, a routine ultrasound scan performed at 28 weeks revealed fetal ascites, bilateral talipes, and oligohydramnios. This woman, married to possibly her first cousin, was at risk for an autosomal recessive disease, a metabolic disorder. At 29 weeks, an amniotic fluid biochemical study revealed the presence of an abnormal band of free sialic acid, leading to a diagnosis of a congenital form of sialic acid storage disease. Termination of pregnancy was performed at 30 weeks. Measurement of free sialic acid in cultured fetal skin fibroblasts confirmed the diagnosis.
Prenatal sonographic diagnosis of autosomal recessive polycystic kidney disease (arpkd) during the early second trimester
Authors: Wisser J. , Hebisch G. , Froster U. , Zerres K. , Stallmach T. , Leumann E. , Schinzel A. , Huch A.
Published: March 2007

Autosomal recessive polycystic kidney disease (ARPKD) is a rare hereditary disease with a high neonatal mortality. Currently, prenatal diagnosis is possible only during the second half of pregnancy, when bilaterally enlarged, echogenic kidneys are visible by ultrasound. We describe a case in which a diagnosis of ARPKD was sought in the first half of pregnancy. High‐resolution ultrasonography revealed echogenic, normal‐sized kidneys at 15+4 weeks. Microsatellite DNA analysis of a chorionic villus sample, parental blood, and blood of an affected sibling showed that the fetus had the maternal haplotype and a recombination of the paternal haplotype. Thus, no distinction between homo‐ and heterozygosity for the ARPKD mutation in the fetus was possible. A further ultrasound examination at 19+4 weeks confirmed the previous results, indicating that the fetus was likely to be affected. After termination of the pregnancy, the diagnosis was confirmed on microscopic examination.
Prenatal diagnosis of ring chromosome 6
Authors: Dawson A. J. , Marles S. L. , Harman C. R. , Phillips S. , Menticoglou S.
Published: March 2007

An amniocentesis was performed on a gravida 1, para 0 23‐year‐old female because of high maternal serum alpha‐fetoprotein and nuchal thickening/cystic mass apparent on the fetal ultrasound. Detailed ultrasound examination revealed multiple anomalies including brain abnormalities. The fetus was found to have a mosaic female karyotype: 45,XX, ‐ 6/46,XX,r(6) (p25q27) (62 per cent:38 per cent). This is the first report of a prenatally diagnosed case of ring chromosome 6.
An investigation of methods for enriching trophoblast from maternal blood
Authors: Johansen Marianne , Knight Marian , Maher Edward J. , Smith Kim , Sargent Ian L.
Published: March 2007

Trophoblast deportation is known to occur in normal human pregnancy, but it is not yet clear whether these cells routinely enter the maternal peripheral circulation and are available as a source of fetal DNA for non‐invasive prenatal diagnosis of genetic disorders. To resolve this issue requires an efficient method of enriching trophoblast from maternal blood combined with a means to confirm its identity. Five different techniques were tested on ten retroplacental blood samples to determine the most sensitive and operator‐efficient method. Lysis of red cells alone gave the best recovery of trophoblast but had to be discounted, together with Ficoll density gradient centrifugation, due to the very low purity and the excessive time required. Fluorescence‐activated cell sorting (FACS) of pre‐enriched trophoblast resulted in the lowest recovery rate (8 per cent) despite a 3250‐fold enrichment and a very high purity. Immunomagnetic beads (Dynabeads) coated with anti‐CD 16 antibody proved to be the best method for the subsequent immunocytochemical characterization of deported trophoblast. However, IO beads coated with anti‐CD45 antibody may be more useful for isolating trophoblast for prenatal diagnosis due to the high purity, enrichment (32‐fold), and recovery rate (78 per cent) obtained with this method.
Detection of fetal cells in transcervical samples and prenatal diagnosis of chromosomal abnormalities
Authors: Adinolfi Matteo , Sherlock Jon , Tutschek Boris , Halder Ashutosh , Delhanty Joy , Rodeck Charles
Published: March 2007

Transcervical samples collected by lavage, aspiration, and cytobrush from women between 6 and 13 weeks of gestation were tested for the presence of fetal cells using fluorescence in situ hybridization (FISH) with probes for chromosomes X, Y, 1, and 21, and by polymerase chain reaction (PCR) amplification of DNA sequences derived from chromosomes X, Y, and 21. With a few exceptions, a good correlation was observed between the results of sexing the fetuses using FISH or PCR on transcervical cell (TCC) samples retrieved by lavage and those obtained by testing fetal (placental) tissue. In a comparative study between TCC samples collected by lavage or cytobrush, the sex of the fetus was correctly diagnosed by PCR amplification of a Y‐derived DNA sequence. Variable results were observed with samples obtained by aspiration, mainly because this procedure was found to be more prone to failure to remove thick mucus without previous injection of physiological saline. Chromosome 21‐derived small tandem repeats (STRs) of fetal origin were successfully detected in about 40 per cent of TCC samples recovered by lavage. Two cases of chromosomal abnormalities, one of trisomy 21 and one of triploidy, were detected in TCC samples in the course of our investigations.