Children who inherit 2 mutated ALPK3 genes have a 25% increased chance of having cardiomyopathy.
In a recent study, researchers discovered a novel disease gene implicated in the development of pediatric cardiomyopathies.
Cardiomyopathy is the deterioration of the heart muscles’ ability to contract. Approximately 40% of children born with cardiomyopathy die within 5 years of diagnosis, according to a study presented at the annual conference of the European Society of Human Genetics.
Researchers described how analyzing the exomes of these children led researchers to the discovery that there was an inherited mutation in the alpha-kinase 3 (ALPK3) gene. Parents who both carry the mutated ALPK3 gene have a 25% risk of having a child with severe cardiomyopathy that will develop early in life.
"However, several family members who carried only 1 mutated gene copy also developed cardiac disease, albeit at a later stage in life," said Johanna Herkert, MD. "The identification of these mutations enables us to provide genetic counselling, predictive testing of family members, and prenatal testing in future pregnancies. It also allows us to provide early treatment, and a potential target for drug development in the future."
Researchers included 5 children from 3 different families, all with different ethnic backgrounds. There were 4 patients diagnosed within hours of birth, and the last patient developed symptoms at the age of 4.
There were 3 children who died between 35 weeks of gestation and 5 days of birth, according to the study. The other patients were 11-years-old, but showed symptoms of severe cardiomyopathy.
"We knew that mice without a functional ALPK3 gene displayed very similar cardiomyopathy related features to those observed in our pediatric patients, but we did not quite know how dramatic its effect would be in humans,” Dr Herkert said. “Our findings show that we now should include this gene in routine diagnostic screening in order to be able to identify affected children and their family members at risk. This will also give us an insight into the prevalence of ALPK3-related cardiomyopathy in the general population."
Researchers are hopeful that the findings from this study can lead to a drug development target for a treatment that could be administered after birth to prevent the disease from developing further, according to the study.
"We are currently studying the effect of the ALPK3 mutations on the production of the protein in heart muscle, but also in skeletal muscle, as ALPK3 gene mutations may result in skeletal muscle problems too. Moreover, a large genome study has shown a possible link between ALPK3 and cardiac hypertrophy, or thickening of the heart muscle. We would like to explore this finding further as it may well mean that ALPK3 is implicated in other heart diseases in the general population, and once again this could suggest new treatment possibilities,” Dr Herkert concluded. "Better knowledge of the precise role of the gene in disease development, as well as the elucidation of the molecular pathways involved, should lead us towards improved clinical care from the point of view of screening and surveillance, and to targeted drug development."