Detection of fetal HLA-DQα sequences in maternal blood: A gender-independent technique of fetal cell identification

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.     

DNA-based carrier detection and prenatal diagnosis of tyrosinase-negative oculocutaneous albinism (OCA1A)

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.     

Maternal age-specific risks for trisomies at 9—14 weeks' gestation

This study provides data on the incidence of fetal trisomies 21, 18, and 13 at 9–14 weeks' gestation in women aged 35–45 years and estimates of maternal age-specific risks in women aged 20–45 years. Our data from 5814 singleton pregnancies undergoing first-trimester karyotyping for the sole indication of maternal age ⩾ 35 years were combined with those from two previous reports and the incidence of the trisomies was calculated from a total of 15 793 pregnancies. Comparison of incidences at 9–14 weeks' gestation with published data at 15–20 weeks' gestation and in livebirths demonstrated that at birth the maternal age-specific incidence of trisomy 21 is 33 per cent lower than at 15–20 weeks' gestation and 54 per cent lower than at 9–14 weeks' gestation. Furthermore, the relative frequency of trisomies 18 and 13 decreases from 30 per cent at 9–14 weeks to 22 per cent at 15–20 weeks and 14 per cent at birth.     

Determinants of parental decisions to abort for chromosome abnormalities

Parental decisions concerning the continuation of pregnancy following prenatal detection of abnormal chromosomes were evaluated for 80 patients whose diagnosis and prenatal counselling were performed in our centre. Twenty-two anomalies were diagnosed by chorionic villus sampling (CVS) and 58 by amniocentesis. The severity of the chromosome anomaly and associated ultrasound findings in the first vs. second trimester were correlated with patients' decisions. No difference was found in the likelihood of parental decisions to interrupt or continue a pregnancy between CVS and amniocentesis for either the‘severe’ or the‘questionable’ group of chromosome anomalies. Ninety-three per cent of patients with severe prognosis and 27 per cent with questionable prognosis opted for pregnancy termination (p <0·0001). The association of ultrasound anomalies and termination was highly significant (p< 0·001). The severity of the chromosome anomaly, and, to a lesser extent, the visualization of anomalies on ultrasound were the major determinants of parental decisions to terminate the pregnancy. The diagnosis of an anomaly in the first trimester was no more likely ito lead to a termination of pregnancy than in the second trimester.     

Dystrophin protein and rflp analyis for fetal diagnosis and carrier confirmation of duchenne muscular dystrophy

A pregnant woman with indeterminate Duchenne muscular dystrophy (DMD) carrier status, but with DMD diagnosed in her deceased brother (unavailable for study), presented for prenatal diagnosis, intending to continue the pregnancy only if proven unaffected with DMD with near absolute certainty. Creatine kinase (CK) assays to clarify carrier status were inconclusive. Male sex in the fetus was identified, but DNA restriction fragment length polymorphism (RFLP) analysis was not yet available to this centre to investigate the possible transmission of the DMD gene, and the pregnancy was terminated. Tissue histology and dystrophin protein analysis demonstrated the absence of DMD. In a situation with proven maternal carrier status, future fetal inheritance of the opposite maternal X chromosome would indicate the presence of DMD. However, maternal carrier status remained in doubt through a second pregnancy, even with RFLP studies, and was finally established when dystrophin analysis confirmed the presence of DMD in the second fetus. Histologic findings are presented, contrasting features in the two fetuses. The value of dystrophin analysis for establishing the diagnosis of fetal DMD, in this case proving maternal carrier status in a difficult situation, and for demonstrating DMD gene:RFLP haplotype relationships is illustrated.     

Prenatal application of fluorescent in situ hybridization (FISH) for identification of a mosaic Y-chromosome marker,IDIC(Yp)

An amniocentesis was performed at 13.3 weeks' gestation for advanced maternal age. A mosaic sex chromosome pattern was found: of 50 cells examined, 34 had a 45,X karyotype. In 14 cells with a modal number of 46, a recognizable Y was substituted by a small non-fluorescent marker. C-banding identified the marker as an isodicentric in 12 cells. In two cells, the non-fluorescent marker appeared to be monocentric and looked like a non-fluorescent del (Yq), but could have been an isodicentric Y with inactivation of one of the centromeres. Two cells with a modal number of 47 showed two copies of the monocentric marker. Fluorescent in situ hybridization with an alpha satellite Y-specific centromeric probe confirmed the Y-chromosome origin of the markers and allowed for more accurate prenatal diagnostic information.     

Getting the ‘pulse’ of your employees: the use of cardiovascular research in better understanding behavior in organizations

Cardiovascular disease has severe consequences for both individual betterment and organizational health. Yet, organization‐based cardiovascular research remains quite limited. This commentary addresses this void by integrating research dating from the famous Hawthorne experiments with current medical science. It then suggests future organizational research on cardiovascular health and recommends use of specific composite cardiovascular measures to advance our understanding of the organizational implications of cardiovascular disease. Copyright © 2006 John Wiley & Sons, Ltd.     

Prenatal diagnosis of thalidomide syndrome

A case of thalidomide syndrome diagnosed by ultrasound in the 17th week of pregnancy is presented. The pregnant woman had leprosy and received adjuvant treatment with thalidomide. The affected fetus was exposed to the drug until the 35th day of pregnancy and presented absent external ears, upper limb phocomelia and absent tibiae and fibulae. No internal organ abnormalities were noticed at autopsy.