Precision Genetic Counselling and Reproduction (PREGCARE)
Precision Genetic Counselling and Reproduction (PREGCARE): Measuring the recurrence risk of serious genetic disorders to inform parental decision-making
University of Oxford
Duration of Study in the UK
2 years, 11 months, 30 days
Genetic conditions sometimes appear “out of the blue” in the child of a healthy couple. Genetic testing shows an alteration in the child’s DNA, which is not - on routine investigation - present in the samples (usually blood) taken from either parent. This situation, in which a misprint has arisen at some stage during the copying of the DNA, is termed a “de novo mutation” (DNM).
Although the DNM may appear to be a one-off occurrence, we know that the same mutation can occasionally occur in another child subsequently born to the same couple. This is caused by the mutation being present in multiple cells of either the eggs or sperm, a process called “mosaicism”.
The overall risk for the condition to recur in another child, because of mosaicism, is ~1-2%. However, the true risk in individual couples might vary from zero to 50%. The purpose of this study is to stratify new mutations into specific mutational categories, in order to give parents who have had a child with a new mutation a modified, more accurate, figure for the actual risk that another child of theirs would be affected with the same genetic condition.
To undertake the study, we would request samples of different tissues from each family member (mother, father, child), to look for mosaicism. Specifically, we propose to obtain a single sample each of blood, saliva and urine from the mother; blood, saliva, urine and semen from the father; and mouth swabs from the affected child and both parents.
Based on prior knowledge, we anticipate that the results would reassure up to 75% of couples that the risk for another child was in fact negligible. In the other 25% the risk would increase, providing important information that would help couples to make better informed decisions in the future.
London - Queen Square Research Ethics Committee
Date of REC Opinion
26 Jul 2017
Further Information Favourable Opinion