New research led by the Institute of Cancer Research in the UK has discovered that a gene mutation associated with leukemia may be the cause of a newly described condition that affects the growth and intellectual development of children.
This is according to a study recently published in the journal Nature Genetics.
To reach their findings, the research team analyzed the genomes of 152 children with overgrowth disorders and their parents, alongside 1,000 controls from the UK population.
Overgrowth disorders are a group of genetic disorders that cause an abnormal increase in body size, as well as intellectual disability and facial dysmorphism. Such disorders already described include Beckwith-Wiedemann syndrome and Weaver syndrome.
The researchers discovered that 13 of the children had mutations in the DNA methyltransferase gene - DNMT3A. All children with these mutations were taller than usual for their age, had intellectual disabilities and shared similar facial features.
However, the team did not find these mutations in the children's parents or controls.
Based on their findings, the research team has called this new condition "DNMT3A overgrowth syndrome."
DNMT3A mutations already exist in certain leukemias
The researchers say the DNMT3A gene is crucial for development. It provides instructions for the creation of DNA (cytosine-5)-methyltransferase 3 alpha - an enzyme that establishes the initial locations for methylation during development. But mutations in the DNMT3A gene prevent it from working properly.
DNMT3A mutations are already known to exist in certain forms of leukemia, including cytogenetically normal acute myeloid leukemia (CN-AML). In this type of leukemia, the DNMT3A mutations are somatic, meaning they are not inherited and are only found in cells that become cancerous.
But the researchers say the mutations discovered in DNMT3A overgrowth syndrome are not the same as those found in leukemia, and there is no evidence that children with DNMT3A overgrowth syndrome have an increased risk of cancer.
Commenting on the findings, study leader Prof. Nazneen Rahman, head of genetics at the Institute of Cancer Research (ICR), says:
"Our findings establish DNMT3A mutations as the cause of a novel human developmental disorder and add to the growing list of genes that appear to have dual, but distinct, roles in human growth disorders and leukemias."
Welcome news for families of children with DNMT3A mutations
The investigators say the results of the study provide good news for the families of children with DNMT3A overgrowth syndrome.
After analyzing the genomes of 152 children with overgrowth disorders, researchers discovered 13 of the children had mutations in the DNMT3A gene.
Not only do the findings present parents with a reason for their child's developmental problems, but the fact that the DNMT3A mutations are not inherited from parents means there is a low risk of other children in the family developing the same condition.
"Having a diagnosis can make a real difference to families," says study co-leader Dr. Katrina Tatton-Brown, clinical researcher at the ICR.
"I recently gave the result back to one of the families in which we identified a DNMT3A mutation and they greatly appreciated having a reason for their daughter's condition after many years of uncertainty."
Furthermore, Dr. Tatton-Brown told Medical News Today that the findings enable health care professionals to have better management of individuals with DNMT3A overgrowth syndrome.
"We are now in a position to better define the syndrome, determine any associated clinical problems and develop appropriate management guidelines for the DNMT3A overgrowth syndrome."
The investigators say DNMT3A is the latest to join an emerging family of genes involved in both overgrowth disorders and hematological malignancies - cancers of the blood, bone marrow and lymph nodes.
With this in mind, they conclude that other genes that are somatically mutated in hematological malignancies - including TET2, IDH1 and IDH2 - may be worth assessing in developmental growth disorders.
Medical News Today recently reported on a study detailing the discovery of genetic mutations that could be a cause of schizophrenia, while other research found genetic mutations that could prevent type 2 diabetes.