12 new genetic causes of developmental disorders identified

Scientists have discovered 12 new genetic causes of developmental disorders such as intellectual disabilities and congenital heart defects in children.
The findings come from Deciphering Developmental Disorders (DDD) in the UK, the world's largest, nationwide and genome-wide diagnostic sequencing programme that will ultimately analyse data from 12,000 families.
The study described results from the first 1,133 samples after researchers sequenced DNA and compared the clinical characteristics of over a thousand children to find the genes responsible for conditions that include intellectual disabilities and congenital heart defects, among others.
DDD, a collaboration between the National Health Service and the Wellcome Trust Sanger Institute, worked with 180 clinicians from 24 regional genetics services across the UK and the Republic of Ireland to analyse all 20,000 genes in each of 1,133 children with severe disorders so rare and poorly characterised that they cannot be easily diagnosed using standard clinical tests.

Researchers collected together clinical information in a database along with the genetic variants from each patient's genome.
If patients who share similar symptoms also have variants in common, it helps to narrow down the search for causative mutations across the genome.

However, this can be challenging, since the chance of having a particular type of mutation can be as low as one in fifty million.
DDD's nationwide secure data-sharing network made it possible to find and compare these incredibly rare disorders; in fact, for four of the 12 newly identified genes, identical mutations were found in two or more unrelated children living hundreds of miles apart, researchers said.

In one example, two unrelated children, both with identical mutations in the gene PCGF2, which is involved in regulating genes important in embryo development, were found to have strikingly similar symptoms and facial features.
This constitutes the discovery of a new, distinct dysmorphic syndrome, researchers said.
All of the newly discovered developmental disorders were caused by new, 'de novo', mutations, which are present in the child but are not in their parents' genomes.