Recent studies have shown that MBNL exhibits differential dose-response relationships across the various gene translation events that it regulates in health and disease. It is as yet unclear precisely how the structure of the pre-mRNA itself contributes to patterning of MBNL-dependent alternative splicing.
Fuchs’ endothelial corneal dystrophy is mechanistically related to and commonly observed in DM1 families even in the absence of the Fuchs’ mutation.
A key driving factor behind DM1 is the instability of expanded CTG repeats in DMPK, resulting in both germline and somatic expansions in repeat length. Variant CCG-containing CTG repeats are more stable and yield a milder phenotype than corresponding “pure” DM1 alleles.
One of the challenges faced by doctors treating patients with myotonic dystrophy type 1 (DM1)—and drug developers designing clinical trials—is the broad difference in the way the disease manifests itself and progresses from patient to patient. MDF Scientific Advisory Committee member Dr. Guillaume Bassez, a neurologist at the Institut de Myologie in Paris, has identified subgroups of the DM population to help address this issue.
MDF strongly encourages patients, families, clinicians, and researchers to respond to the NIH’s Request for Information on the Wellstone Center Program.