Researchers from the United Kingdom revealed on Dec. 24 that they have identified 12 genes that cause development disorders in children, based on the initial results of a long-term program known as Deciphering Developmental Disorders (DDD).
The project uses new genetic technologies with the objective of shedding light on why certain individuals have developmental disorders. The study aims to collect DNA and clinical information from 12,000 undiagnosed children, who have developmental disorders, and their parents.
"It could significantly improve our understanding and management of these rare conditions and provide new avenues of research into treatments for scientists to pursue," said DDD program clinical lead Helen Firth.
The DDD project, which started in 2010, has so far analyzed the genes of 1,133 children with rare developmental disorders and their parents, a small fraction when compared with the goal of sequencing the genes of 12,000 families, but the study has already led to the discovery of 12 genetic causes of developmental disorders.
"Using a combination of exome sequencing and array-based detection of chromosomal rearrangements, we discovered 12 novel genes associated with developmental disorders," Firth and colleagues wrote in their report published in the journal Nature on Dec. 24. "These newly implicated genes increase by 10% (from 28% to 31%) the proportion of children that could be diagnosed."
Four of these genetic causes were discovered after researchers observed identical mutations in at least two unrelated children who live far from each other. Researchers also found a new and distinct dysmorphic syndrome after assessing two unrelated children who both have identical mutations in the PCGF2, which regulates genes that play a crucial role in embryo development, and who exhibit remarkably similar symptoms and facial features.
Each of the newly discovered developmental disorders were found to have been caused by de novo mutations, or mutations that were present in the child but not in the parents' genome. This finding indicates the importance of using the genetic data of the patient's parents, who do not have a developmental disorder, as this allows the researchers to filter out inherited benign mutations when looking for the cause of the child's condition.
With the aim of expanding their work, the DDD team is sharing limited and anonimyzed genetic and clinical data of the patients through the DECIPHER database, with the hope that other clinical and research programs from other parts of the globe deposit data into the database. The initiative could pave the way for the identification of more genetic causes of developmental disorders.
