Genetic aspects of miscarriage

Fetal chromosome abnormalities account for about 50% of first-trimester pregnancy losses. Most of these abnormalities are numerical abnormalities (86%) and a low percentage is caused by structural abnormalities (6%) or other genetic mechanisms, including chromosome mosaicism (8%). The recurrence risk of numerical abnormalities is low, so karyotyping of fetal material in case of a miscarriage does not seem worthwhile in daily practice. Half of the structural abnormalities may be inherited from a parent carrying a balanced chromosome translocation or inversion. Parental carriership is found in 4-6% of the couples with recurrent miscarriage. In case of parental carriership of a balanced structural chromosome abnormality, a next pregnancy may result in a child with an unbalanced structural chromosome abnormality. This child can have multiple congenital malformations and/or a mental handicap. Prenatal diagnosis is therefore recommended. Conventional laboratory techniques, such as tissue culturing and karyotyping, or (semi-)direct chromosome technique of chorionic villi, and the recently developed laboratory techniques such as fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH), are described successively. Until now, not enough evidence has been available about the role of other genetic mechanisms, such as single-gene abnormalities, uniparental disomy, genomic imprinting, multifactorial disorders and skewed X chromosome, in the occurrence of miscarriage

Is placental mosaicism associated with poor perinatal outcome?

In 37 pregnancies with placental mosaicism detected at first-trimester chorionic villus sampling in 2000 pregnancies, two pregnancies (5.4 per cent) ended in a spontaneous abortion at 15 weeks (46,XX 47,XX, + 16) and in a perinatal loss in a term pregnancy (46,XY/47,XY, + 10), respectively. The outcome of the other 35 pregnancies was normal. The total pregnancy loss rate before 28 weeks in the first 1000 pregnancies was previously reported to be 3.6 per cen

Prenatal diagnosis in the Netherlands. Dutch Working Party of Prenatal Diagnosis

Prenatal invasive diagnosis of genetic conditions in the Netherlands is well organised, based on uniform indications and has a sound financial structure. Facilities for fetal karyotyping and DNA analysis are available in the 8 academic centres. Prenatal diagnosis of metabolic diseases is mainly carried out in Rotterdam. Amniocentesis, transcervical and transabdominal chorionic villus sampling are carried out in all centres, including 4 subcentres. The national Working Party on Prenatal Diagnosis started in 1985 and is a useful platform for all obstetricians and geneticists involved in prenatal diagnosi

De ontrafeling van het humane genoom: een mijlpaal, geen eindstreep

The base sequence of the entire human DNA will be known within only a few years. So far, 16,000 of an expected total of 100,000 genes have been identified. Nowadays there are different stages of molecular unraveling: from fully sequenced genes, including mutations responsible for diseases, down to 'predicted' genes for which no corresponding protein is yet known. Moreover, the genes responsible for many monogenetic conditions have not yet been identified. The revolutionary approach of at random cloning and sequencing was shown to be successful in the recently published genome sequence of the fruit fly. The next landmark will be an overview of the characteristics and activity of every protein that this organism can synthesize. However, protein technology has developed less far than DNA-technology and will be subject of the next projec