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Gene causing late foetal death identified

23 January 2015

The research group behind the study.

The research group behind the study.

Researchers at SciLifeLab, Uppsala University and Uppsala University Hospital have identified a gene which can cause foetal deaths at a late stage of pregnancy. The results can be used to help families get answers when a child has died, as well as providing prenatal diagnostics to families who have previously lost a child.

Late foetal deaths, i.e. foetal deaths after pregnancy week 28, occur about four times per 1000 child-births in Sweden.

‘There are several causes of fetuses dying in the womb, for instance diseases in the mother, infections, problems with the placenta or umbilical cord, chromosome abnormalities and congenital disorders. In as many as 50 per cent of the children that die before birth, the underlying reason is unclear’, says Karin Eurenius, senior physician at Uppsala University Hospital and one of the co-authors of the study.

The gene which has now been identified causes a syndrome called FADS, which causes the muscles to stop working. It is characterised by reduced foetal movements, reduced foetal growth, abnormal facial features and under-developed lungs. Most affected children die in the womb or soon after birth due to their lungs not working properly.

In the current study the researchers have used modern sequencing methods to identify the mutation causing the disease. The researchers studied a Swedish family where all children but one had died from FADS, but no previous genetic disorders were known. The researchers studied the DNA of the mother, the father and the foetuses that had died and found a mutation in a gene called MuSK. The mutated gene was found in all family members, but the parents had only one copy each and had therefore not developed the disease. All the afflicted foetuses had two copies of the mutated gene.

The researchers don’t know how common this mutation is in the Swedish population, but since it hasn’t previously been found it is presumed to be quite rare.

‘For a foetus to develop the disease it must inherit a mutated variant from each parent, and the chance of two people with the mutated gene meeting can be regarded as quite small. We are currently investigating the frequency of this mutation in the Swedish population, specifically screening for MuSK in the area where we identified the mutation’, says researcher Maria Wilbe at the Department of Immunology, Genetics and Pathology.

The protein coded for by the MuSK gene is rendered non-functional by the mutation. This causes signal transfers between nerve cells and muscle fibers to not work as they should, which could explain the symptoms observed from FADS. Previous studies have also shown that mice which lack the MuSK gene completely have similar symptoms to children with FADS.

‘With this study we hope to contribute to helping families who have suffered prenatal deaths due to FADS, by making correct genetic diagnoses possible. We also hope to enable early foetal diagnostics for affected families’, says Professor Marie-Louise Bondeson, clinical geneticist at Uppsala University Hospital, who has led the study.

Full article: MuSK – a new target for lethal fetal akinesia deformation sequence (FADS)