DIDA (DIgenic diseases DAtabase) is a novel database that provides for the first time detailed information on genes and associated genetic variants involved in digenic diseases, the simplest form of oligogenic inheritance. The database is accessible via http://dida.ibsquare.be and currently includes 213 digenic combinations involved in 44 different digenic diseases. These combinations are composed of 364 distinct variants, which are distributed over 136 distinct genes. The web interface provides browsing and search functionalities, as well as documentation and help pages, general database statistics and references to the original publications from which the data have been collected. The possibility to submit novel digenic data to DIDA is also provided. Creating this new repository was essential as current databases do not allow one to retrieve detailed records regarding digenic combinations. Genes, variants, diseases and digenic combinations in DIDA are annotated with manually curated information and information mined from other online resources. Next to providing a unique resource for the development of new analysis methods, DIDA gives clinical and molecular geneticists a tool to find the most comprehensive information on the digenic nature of their diseases of interest.

Physical examination including a thorough neurological examination did not reveal important differences between the two groups. Major congenital malformations were significantly more frequent in the ICSI group. However, most of them were corrected by minor surgery. Further monitoring of these children at an older age is recommended.

A total of 199 patients participated in the oocyte donation programme in 336 replacement cycles in whom 69 clinical pregnancies were achieved, of which 53 reached term and delivery. Data concerning the evolution and outcome of pregnancies were retrieved in 52 cases, which involved 39 women with ovarian failure and 18 with functional ovaries. The most frequent complications of pregnancy were uterine bleeding in the first trimester in 18 cases (34.6%), hypertension in 17 (32.7%) and intra-uterine growth retardation (IUGR: 11.5%). These complications were more prominent in twin pregnancies. The Caesarean section rate was 63.5% and a high percentage of elective sections (54.5%) was observed. Of singleton pregnancies, 54.6% had a birth weight of > 3000 g at full term (> 37 weeks), while 62.5% of twins weighed between 2000 and 3000 g. One intra-uterine death occurred, so that the perinatal mortality was 1.7% and one newborn was operated on for stenosis of the pulmonary artery, while the incidence of premature labour was low (1.9%). A comparison of complications between pregnancies associated with ovarian failure and with functional ovaries revealed a higher frequency of bleeding in the first trimester (38.2% and 27.8% respectively) and of hypertension (38.2% and 22.2% respectively) in those with ovarian failure, although the differences were not statistically significant. In conclusion, women who become pregnant after oocyte donation and especially those with ovarian failure should be considered as high-risk obstetric patients.

In order to evaluate the safety of the intracytoplasmic sperm injection (ICSI) procedure, a prospective follow-up study of 423 children born after ICSI was carried out. The aim of this study was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones. Before starting the infertility treatment, couples were asked to participate in a follow-up study including genetic counselling and prenatal diagnosis. The follow-up study of the child was based on a visit to the paediatrician-geneticist at birth or at 2 months of age, at 1 year and at 2 years of age when a physical examination for major and minor malformations and a psychomotoric evaluation were done. Between April 1991 and September 1994, 320 pregnancies obtained after ICSI led to the birth of 423 children (222 singletons, 186 twins and 15 triplets). Prenatal diagnosis determined a total of 293 karyotypes, one of which was abnormal (0.3%), and four were benign familial structural aberrations, all inherited from the paternal side. A total of 14 (3.3%) major malformations were observed, defined as those causing functional impairment or requiring surgical correlation. Neurological or developmental problems at the age of 2 months were found in 14 children, four of whom were multiples. Compared to most registers of children born after assisted reproduction and to registers of malformations in the general population, the figure of 3.3% major malformations is within the expected range. Before drawing any firm conclusion, further careful evaluations of the available data are necessary.

Background: Predictive genetic testing has high impact on cancer prevention for BRCA carriers and passing this information in BRCA families is important. Mostly, this is proband-mediated but this path is defective and denies relatives lifesaving information. Objective: To assess the efficacy/safety of an intervention, in which relatives are actively informed. Design: Sequential prospective study in new BRCA families. The proband informed relatives about predictive testing (phase I). After 6 months, a letter was sent to adult relatives who had not been reached (phase II). Then a phone call was made to obtain a final notion of their wishes. All subjects received psychometric testing (State-Trait Anxiety Inventory, STAI), an interview and routine counselling. Results: Twenty families were included. Twenty-four of the relatives could not be reached, 59 were ‘decliners’, 47 participated by the proband and 42 by the letter. Predictive testing was performed in 98 % of the participants of which 30 were mutation carriers. The intervention is psychologically safe: the 95 % CI for the estimated mean difference in STAI DY1 between phase II/I subjects (mean difference −1.07, 95 % CI −4.4 to 2.35, p = 0.53) shows that the mean STAI DY1 score (measured at first consult) for phase II is no more than 2.35 units higher than for phase I, which is not relevant. Conclusions: A protocol directly informing relatives nearly doubles the number of relatives tested and is psychologically safe. This should lead to a change in counselling guidelines in families with a strong germline predisposition for cancer.Electronic supplementary materialThe online version of this article (doi:10.1007/s10689-015-9854-4) contains supplementary material, which is available to authorized users.

Human chorionic gonadotrophin beta (HCG-beta) is a trophoblast marker. Its expression is normally limited to syncytiotrophoblast cells of chorionic villi, although it is known to be secreted from the human embryo as early as 7 days post-fertilization. To examine the onset of embryonic transcriptional activity of the gene encoding this polypeptide we have performed in-situ hybridization to cellular RNAs of human tripronucleate preimplantation embryos. We see expression of HCG-beta RNA at the 6-8-cell stage, before morphological differentiation between trophectoderm and inner cell mass is apparent. We believe that this RNA is the product of de novo transcription from the embryonic genome, since transcripts are only observed in embryos of at least 2 days post-fertilization in age.

This study was supported by Methusalem grants and by grants from Wetenschappelijk Fonds Willy Gepts, all issued by the Vrije Universiteit Brussel (VUB). All co-authors except M.B. and H.T. declared no conflict of interest. M.B. has received consultancy fees from MSD, Serono Symposia and Merck. The Universitair Ziekenhuis Brussel (UZ Brussel) and the Centre for Medical Genetics have received several educational grants from IBSA, Ferring, Organon, Shering-Plough and Merck for establishing the database for follow-up research and organizing the data collection. The institution of H.T. has received research grants from the Research Fund of Flanders (FWO), an unconditional grant from Ferring for research on testicular stem cells and research grants from Ferring, Merck, MSD, Roche, Besins, Goodlife and Cook for several research projects in female infertility. H.T. has received consultancy fees from Finox, Abbott and ObsEva for research projects in female infertility.

25 June 2012.