Neuromuscular disease diagnosis gives long awaited answers to families
When Shirley Corrigan and her siblings were growing up in Ireland their friends thought they were clumsy, but nobody knew why.
“I was always falling over and I broke my arm 4 or 5 times,” Shirley said. ”My brother Trevor and I had long arms so our sleeves were always too short and when I was 13 I got terrible cramps in my hands and would drop things.”
Now settled in Perth, Shirley and Trevor have both been diagnosed with Charcot-Marie-Tooth (CMT) disease and a scientist from the Harry Perkins Institute of Medical Research has discovered they and their relatives carry a gene which affects only five families in the world.
Shirley’s diagnosis, followed by the diagnosis of her son by Associate Professor Phillipa Lamont in the Neurogenetic Unit at Royal Perth Hospital, meant that that a trip to Ireland last year was more than just a holiday. Shirley urged her Mother, Aunt, Uncle and elder sister to donate DNA samples which she posted back to Perth for analysis by the Perkins Laboratory for Molecular Genetics, headed by Professor Nigel Laing.
After the family’s DNA passed through customs, it was sequenced in Perth using next generation technology at the LotteryWest State Biomedical Facility Genomics at Royal Perth Hospital and was analysed by Royston Ong from the Laing Laboratory at Perkin’s Nedlands campus.
Despite different physical symptoms, the relatives Shirley suspected of having Charcot-Marie-Tooth (CMT) disease were diagnosed positively with the condition, which affects the peripheral nerves.
“This one special gene only known to affect five families spread across the world, France, Ireland, Taiwan and Australia has been traced back to our French descendants hundreds of years ago,” Trevor explained.
“We’ve always known that our family roots included French Protestants who migrated to Ireland in about the 16th Century. Many of our relatives lived in County Laois, south-west of Dublin and it’s well known for its French influence. Both genders on our Mother’s side have showed classic symptoms such as small ankles and muscle wastage and now that we have this genetic information, it all makes sense,” he said.
“Our job is to develop better diagnostics for patients with CMT,” Professor Laing said. “So far there are around 60 genes known to cause Charcot-Marie-Tooth disease and we expect there’ll be more.”
“It’s been a difficult disease to diagnose because the disease is sometimes dominant, sometimes recessive, sometimes X-linked and there’s a huge range of symptoms. Not every family member gets CMT. We are definitely continuing to work on this over the next five years,” Professor Laing said.
Professor Laing’s laboratory is one of only four outside Europe to be partners in a European Union project called “NEUROMICS” to find for neurogenetic diseases new genes and develop next generation diagnostics, (which is a new, faster way to sequence DNA. The other three labs are in North America. It was announced last month that Professor Laing’s laboratory will receive a NHMRC European Union Collaboration Grant to fund his laboratory’s part of the project.
“It’s a great honour to have our lab at Perkins in Perth recognised as being a leader in this field,” Professor Laing said.
Mr Ong said it was very rewarding to find answers for families.
“We don’t have a cure for this disease so if you can give a family an answer, it gives them something to work on,” he said.
The Irish families affected by CMT say that it’s good to finally know why they have symptoms including muscular cramps, severe leg pain and numb toes as well as problems tilting their feet when walking, which makes it easy to trip over.
“Knowing this hasn’t stopped us from working, but it means you can choose your job and your activities,” Trevor says. “We’re very conscious of the need to get out and keep our legs moving, and Shirley knows she needs to pay attention at all times to prevent falls.”
The brother and sister, who each have two children of their own, also believe that early diagnosis of the condition may help future generations to tackle their problems at an earlier age using physiotherapy and orthotics.
To read more about the Perkins neurogenetic research click here.