Genetic Variant in Duchenne MD Linked to Earlier Loss of Ambulation, Study Finds

The expressivity of Mendelian diseases can be influenced by factors independent from the pathogenic mutation: in Duchenne muscular dystrophy (DMD), for instance, age at loss of ambulation (LoA) varies between individuals whose DMD mutations all abolish dystrophin expression. This suggests the existence of trans-acting variants in modifier genes.

DMD is caused by mutations in the gene that encodes dystrophin, a protein that plays an important role in the proper functioning of muscle cells. However, changes in the coding sequence of certain genes – changes which are called polymorphisms – may influence the development of the disease in patients, and are called disease modifiers.

Previous studies have identified polymorphisms in two genes – SPP1, encoding osteopontin, and LTBP4, encoding TGFβ-binding protein 4 – establishing them as Duchenne MD modifiers. To identify other DMD modifiers that could influence the when ambulation is lost in patients; researchers analyzed the DNA of a group of 109 Duchenne patients with European or European-American ancestry from the Cooperative International Research Group Duchenne Natural History Study. The team focused on 438 polymorphisms in 384 genes previously implicated in DMD.

A minor variant, known as rs1883832, was found on the CD40 gene, which encodes a protein of the immune system. This variant causes a reduction in the expression levels of the protein, altering the function of the immune system. It was associated with an earlier loss of ambulation in patients who carried it.


Source : Belo et al., 2016