Large Study Finds 14 New Genetic Disorders in Children

Congenital anomalies are a leading cause of death among infants worldwide, and genetic factors play a major role in most of the cases. One of the largest genetic studies to be carried out in children has just uncovered 14 new genes responsible for developmental disorders.

Congenital anomalies are responsible for the death of more than 300,000 infants worldwide. These anomalies often include developmental disorders, including neural tube defects, heart defects, autism, Down syndrome, or other forms of intellectual disability.

For over 50% of these anomalies, researchers do not yet know the cause but do know that genes play a key role.

There are currently more than 1,000 recognized genetic causes for some of the developmental disorders. However, given that most developmental disorders are very rare, many more pathogenic variants remain unknown, medicalnewstoday.com reported.

The Deciphering Developmental Disorders (DDD) study aimed to identify developmental disorders in children, and use genomic technologies to improve diagnosing.

DDD is the largest genetic study of children with previously undiagnosed developmental disorders to date. It involved 200 clinical geneticists from the National Health Service (NHS) in the United Kingdom. They examined more than 20,000 human genes, and included children from around 4,000 families from the UK and Ireland.

The results have been published in the journal Nature.

The study was carried out by researchers from the Wellcome Trust Sanger Institute in Cambridge, and it was co-led by Dr. Matthew Hurles and Jeremy McRae.

 Exome Sequencing

Research involved the exome sequencing of 4,293 families that had at least one member with a severe but undiagnosed developmental disorder.

Exome sequencing is a common and effective way of selectively sequencing the protein-coding regions of the DNA in order to discover genetic variations associated with disorders.

In the sequencing, the team focused on spontaneously arising mutations that occur when the DNA is passed on from parents to children. These mutations - also called de novo or new mutations - are not present in either parent, but appear for the first time in one family member. This is a result of a variant in the sperm or egg of the parent, or in the fertilized egg itself.

The results of the study revealed 94 genes that were particularly likely to have de novo mutations. Of these, 14 genes had not been previously recognized in developmental disorders.

Overall, the team report that between one in 213 and one in 448 children are affected by new mutation-induced developmental disorders. Worldwide, this means that almost 400,000 newly born children are affected by spontaneous mutations.

Professor David FitzPatrick - a supervising author based at the MRC Human Genetics Unit at the University of Edinburgh, UK - emphasized the benefits of the study for potential treatment and prevention.

“Families search for a genetic diagnosis for their children, as this helps them understand the cause of their child’s disorder. This can help doctors better manage the child’s condition, and gives clues for further research into future therapeutics.

In addition to this, a diagnosis can let parents know what the future holds for their child and the risk of any subsequent pregnancies being affected with the same disorder, which can be an enormous help if they want a larger family.”