Background: Analysis of fetal DNA in maternal plasma has recently been introduced as a new method for noninvasive prenatal diagnosis, particularly for the analysis of fetal genetic traits, which are absent from the maternal genome, e.g., RHD or Y-chromosome-specific sequences. To date, the analysis of other fetal genetic traits has been more problematic because of the overwhelming presence of maternal DNA sequences in the circulation. We examined whether different biochemical properties can be discerned between fetal and maternal circulatory DNA. Methods: Plasma DNA was examined by agarose gel electrophoresis. The fractions of fetal and maternal DNA in size-fractionated fragments were assayed by real-time PCR. The determination of paternally and maternally inherited fetal genetic traits was examined by use of highly polymorphic chromosome-21-specific microsatellite markers. Results: Size fractionation of circulatory DNA indicated that the major portion of cell-free fetal DNA had an approximate molecular size of <0.3 kb, whereas maternally derived sequences were, on average, considerably larger than 1 kb. Analysis of size-fractionated DNA (<0.3 kb) from maternal plasma samples facilitated the ready detection of paternally and maternally inherited microsatellite markers. Conclusions: Circulatory fetal DNA can be enriched by size selection of fragment sizes less than ϳ0.3kb. Such

The monogenic etiology of most severe fetal anomaly syndromes is poorly understood. Our objective was to use exome sequencing (ES) to increase our knowledge on causal variants and novel candidate genes associated with specific fetal phenotypes. We employed ES in a cohort of 19 families with one or more fetuses presenting with a distinctive anomaly pattern and/or phenotype recurrence at increased risk for lethal outcomes. Candidate variants were identified in 12 families (63%); in 6 of them a definite diagnosis was achieved including known or novel variants in recognized disease genes ( MKS1, OTX2, FGFR2 , and RYR1) and variants in novel disease genes describing new fetal phenotypes ( CENPF, KIF14 ). We identified variants likely causal after clinical and functional review ( SMAD3, KIF4A , and PIGW ) and propose novel candidate genes ( PTK7, DNHD1 , and TTC28 ) for early human developmental disease supported by functional and cross-species phenotyping evidence. We describe rare and novel fetal anomaly syndromes and highlight the diagnostic utility of ES, but also its contribution to discovery. The diagnostic yield of the future application of prenatal ES will depend on our ability to increase our knowledge on the specific phenotype–genotype correlations during fetal development.

Background: Increased concentrations of cell-free DNA have been found in several disorders and have been interpreted as evidence of increased rates of cell death or turnover. Evidence from in vitro and animal experiments suggests that DNA may play a role in the pathogenesis of rheumatoid arthritis (RA). Methods: We measured cell-free DNA in plasma and serum from patients with RA and healthy controls by use of quantitative PCR for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) DNA. We used protein G Sepharose TM bead adsorption of plasma and elution to isolate antibody-bound DNA. Results: In paired plasma and serum samples of 16 healthy controls the median GAPDH copies were 4500 genome equivalents (GE)/mL plasma (range 319 -21 000) and in 26 RA patients 17 000 GE/mL plasma (2100 -2 375 000, P ‫؍‬ 0.0001). In the serum from normal controls the median GAPDH copies were 35 000 GE/mL (1700 -239 000) and from RA patients 222 000 GE/mL (21 000 -2 375 000, P ‫؍‬ 0.004). A median of 81% of the cell-free DNA in RA was associated with antibody compared with 9% in healthy controls (P ‫؍‬ 0.001). The concentrations of DNA did not vary with the type of therapy patients received.

Background: During peri- and postmenopause there is a high prevalence of psychological symptoms such as emotional instability, depressive moods, anxiety, sleep disorders, and sexual dysfunction. Aetiologically relevant factors for discomfort are decline of sex hormones and psychosocial factors such as lifestyle, attitude towards menopause, pre-menopausal mental health and sociocultural factors. In contrast to the relevance of psychosocial factors, there are few studies on psychological interventions. The present study evaluates an open trial of cognitive-behavioural group intervention consisting of psychoeducation, group discussion and coping skills training for women suffering from climacteric symptoms. Methods: Thirty women were enrolled in this first trial. Standardised (MRS, HADS-D, Partnership Questionnaire, McCoy Female Sexuality Questionnaire) and especially developed (‘Attitudes Towards the Menopause’) instruments were administered 3 times, twice before (T1 and T2) and once after the group intervention (T3). General linear model repeated measures were used to analyse changes in questionnaire measures. Results: Taking the average of the two pre-intervention scores, significant improvements were observed in anxiety (p < 0.01), depression (p < 0.02), partnership relations (p < 0.02), overall score of sexuality (p < 0.02), hot flashes (p < 0.01) and cardiac complaints (p < 0.01) from pre- to post-intervention. No changes were found for sexual satisfaction and stressfulness of menopausal symptoms. Conclusions: This pilot study points at a possible effectiveness of cognitive-behavioural interventions for the treatment of climacteric syndrome. Further studies will have to use randomised trials, comparing different treatments (HRT, phyto-oestrogens, relaxation training, discussion groups) for their effectiveness.

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