A specific mutation in a small RNA molecule called miR-149 was found to be linked to both age of onset and severity in patients with Charcot-Marie-Tooth disease type 1A (CMT1A), according to researchers.
Their study, “Association of miR-149 polymorphism with onset age and severity in Charcot-Marie-Tooth disease type 1A,” was published in the journal Neuromuscular Disorders.
CMT1A is the most common form of CMT type 1. It is characterized by the duplication of the PMP22 gene. While the cause of the disease is uniformly shared by the majority of patients, its onset and progression can be very diverse. The reason behind this diversity is not yet fully understood.
A team led by researchers at Kongju National University in South Korea investigated the role of a small RNA molecule in the regulation of PMP22 levels and its impact on CMT1A outcomes.
Using computer-based analysis methods, the team predicted that the micro RNA molecule miR-149 could target many CMT-related genes including PMP22, MPZ, SPTLC2, SH3TC2, LITAF, ARHGEF10, DHTKD1, DNAJB2, KIF1B, LRSAM1, and NDRG1.
Also, sequencing data from 302 Korean individuals and public databases revealed a genetic variant, identified as rs2292832, in the end-part of the miR-149 precursor sequence.
The team focused on the relevance of miR-149 and its mutation on the clinical features of 176 CMT1A Korean patients with PMP22 duplication.
The patients were divided into two groups according to age of disease onset: younger than 20 (early-onset), and 20 or older (late onset).
The miR-149 variant was found to be more frequently found among patients with late-onset disease. Indeed, the presence of the mutations was associated with a 1.73 increased chance of having late-onset CMT1A.
Interestingly, the frequency of the miR-149 variant was found to be higher among patients with late-onset disease with mild manifestations rather than any patients with late-onset, severe disease, or early-onset disease.
“From this study, we observed that rs2292832 was closely associated to the onset age and severity of CMT1A,” the researchers wrote.
Although the team did not evaluate the direct interaction between miR-149 and the PMP22 gene, they believe this variant “is a potential candidate as a genetic modifier” that can regulate the outcome variability of CMT1A.
“This study may provide the first evidence that polymorphism [a single nucleotide variant] in the miR gene is associated with the CMT1A [presentation],” they added.