UWA researchers unravel rare form of distal myopathy

UWA Centre for Medical Research scientists have unravelled the mystery of a rare form of distal myopathy, a muscle wasting disease affecting the feet and hands.

According to research leader Dr Rachael Duff, the rare myopathy uncovered in a family in Victoria “has never before been documented by clinicians or identified in the literature”.

The disease, known as Distal ABD-filaminopathy or William’s myopathy, belongs to the group of distal myopathies gradually onsetting around middle age.

“In some people with distal myopathy, the first muscles affected might be in the feet or the calves, but [in our family] it was the front of the calf and the hands – a particular muscle in the hand specific [William’s myopathy],” Dr Duff says.

The disorder was nicknamed ‘William’s myopathy’ after Dr David Williams, the Victorian clinician who identified in disorder in the family.

The research team sequenced the family’s FLNC gene that encodes the Filamin-C protein (as it is often associated with myofibrillar myopathy) and they identified a mutation.

The ‘ c.752T>C (p.Met251Thr)’ mutation occurs in the N-terminal actin-binding domain, meaning the mutant Filamin-C does not bind properly to another important muscle protein – actin.

“The gene is part of the contractile unit of the muscle and actin is closely involved in the contractile structure. Filamin C then binds on the end,” Dr Duff says.

“So now we have determined that it doesn’t bind properly, we are hypothesising that this is what is causing the problem in muscle function.”

Researchers can confirm the structural mutation through a microscope. Dr Duff says if you cannot confirm the structural mutation patients can be CT scanned and the muscles affected will be noticeable as they are replaced by fatty tissue.

However, unfortunately because the disorder is so rare it is not yet feasible to undertake treatment research.

Instead, Dr Duff says this research significantly aids affected families in genetic counselling so they may determine what kind of pregnancy choices they may chose to make in the future.

“And the other thing is studying even rare muscle diseases opens up new understandings of how muscles function as we still don’t really know the complete picture.”

“It’s not until things go wrong that we can know more about muscle function.

“We didn’t know Filamin-C would have such a huge impact in muscle function, so this may even help potential targets for other diseases.”

By Laura Glitsos

(Source: Science Network Western Australia: American Journal of Human Genetics)