A new skeletal disease discovered through microRNA study
In Sweden, researchers at the Karolinska Institute have detected a mutation in a microRNA that can lead to a new skeletal disease. The alteration found in this microRNA results in a gain-of-function of the microRNA. It is the first time that a mutation of this type is related to a disease.
The study was based on the analysis of the genome of two families unrelated to three patients presenting symptoms indicating a new skeletal disorder: short stature, short limbs, small hands and feet, and characteristic facial features. The researchers found a nucleotide change in the gene responsible for producing the microRNA, named miR140. The change appeared exclusively in all three patients and was absent in the rest of the members of both families. This, together with the transmission pattern and the fact that mutations in miR140 produce short stature and craniofacial anomalies in mice, led to the suspicion that the mutation could be the molecular cause of the pathology observed. Using the CRISPR tool – genome editing using “molecular scissors” capable of cutting any DNA molecule in a very precise and fully controlled manner – lines of mice with the same mutation were created and it was confirmed that gain-of-function mutation in miR140 was responsible for the syndrome observed in patients.
MicroRNAs are small RNA molecules that interact with the messenger RNA (mRNA) of genes and can block their expression. One of its functions is to regulate the expression of genes and their intervention in numerous cellular processes is crucial. This is why in recent years they have acquired a special interest in the field of genetic medicine, especially as biomarkers of diseases. The case of this new skeletal disease is a clear example of how the mutations that generate certain pathologies are not always found in genes but can occur in the elements that regulate their expression. Knowing the genome in its entirety, beyond the genes, increases our knowledge about genetic diseases and can help to find currently unresolved congenital disorders and new treatments.
Access to the original article: Gain-of-Function Mutation of MicroRNA-140 in Human Skeletal Dysplasia | Nature Medicine