Fetal abnormalities occur in about 2 to 5 percent of pregnancies but current diagnostic methods such as ultrasound can only give diagnoses in about 40 percent of those cases.
The new research, which was published in Genetics in Medicine showed that, following careful selection of cases by expert genetic review, rapid exome sequencing gave a definitive molecular diagnoses in 81%. Exome sequencing is a genomic technique for sequencing all of the protein-coding genes in a genome and whilst we already knew this method could be used to improve prenatal diagnosis, this study has shown that it is possible to deliver results fast enough to inform pregnancy management.
The research was led by GOSH Biomedical Research Centre researcher Professor Lyn Chitty who is also Professor of Genetics and Fetal Medicine at the UCL Great Ormond Street Institute of Child Health and Consultant at Great Ormond Street Hospital.
In the study, DNA samples from pregnant women and fetuses were sequenced using the rapid exome sequencing method and the results compared to a panel of 240 genes known to cause bone malformations. The women had all been identified as carrying a fetus with suspected skeletal abnormalities following an ultrasound scan. The turnaround times from receipt of samples in the laboratory to diagnosis ranged from 11 to 41 days, with times decreasing as the method was streamlined. In total 16 cases were sequenced and a definitive molecular diagnosis was made in 13 of these patients
The findings have important implications for pregnancy management and prenatal counselling for parents following the detection of unexpected abnormalities.