Gene detectives Bar Harbor lab unraveling rare disorder using Maritimes genealogy

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Jackson Laboratory scientist Jan Marshall spreads a tattered 6-foot-wide genealogical map across two small tables. She’s been laboring on it since the mid-1990s.

At the top of the family tree are two French names, Phillipe Muise D’Entremont and his wife, Madeline H’elie, Acadian settlers in 17th century Nova Scotia. At the bottom are living family members, including the Surettes and their distant cousins the Muises from near Yarmouth, Nova Scotia.

The map, created by Marshall, is the centerpiece in the world-renowned genetics laboratory’s unusual investigation of Alstrom syndrome, a rare disorder that has afflicted Acadian families for centuries. Here and there throughout the tree are individuals who either have been diagnosed or who are believed to have suffered from the illness, which was formally identified and named in 1959.

Alstrom syndrome remains so rare today that only 187 people in the world are known to have the condition. Nine cases – five in the Maritime Provinces and four in New England – have been identified by Jackson Lab researchers. The symptoms include light sensitivity, blindness, deafness, obesity and heart problems. It often leads to an early death.

Unlike investigations into more common disorders, this inquiry required Marshall and other Jackson Lab researchers to identify family members associated with victims, most of whom are dead, and then to traipse across the Maritimes interviewing them and taking blood samples to get DNA.

“My husband used to kid me that I should be sent to Nova Scotia with a shovel,” says Marshall.

In May, Jackson Laboratory scientists announced in a scientific journal that they had identified the gene responsible for Alstrom. Now they are working to understand how it works.

The search’s roots date back to late 1991. It began with a few Jackson Lab researchers’ interest in obesity and diabetes, recalls Patsy M. Nishina, one of the project’s lead scientists.

They were looking for people with those problems at the Center for Human Genetics, a Bar Harbor organization that counsels people with genetic disorders. Two little girls from Nova Scotia with Alstrom syndrome recently had visited the center and the Jackson Lab scientists were intrigued.

That studying this rare disease might lead to findings useful in understanding obesity and diabetes initially was a tough sell to funding organizations, however. Hardly anyone had heard of Alstrom syndrome. But Jurgen Naggert, a principal investigator and husband of Nishina, said the laboratory successfully argued that the size of the extended Acadian family at the center of the research gave scientists enough genetic sources for a statistically meaningful study. Funding was made available by the American Diabetes Association, the National Institutes of Health and other groups.

The project was unusual for Jackson Lab because from the outset it relied so heavily on research on humans instead of mice. And the interactions with affected individuals provided the scientists unusual insight into the lives of those they wanted to help.

“Meeting the kids can grab your heart,” Marshall says.

She’s known Cheryl Surette for seven years. Today, there’s clearly a strong bond between the two, who live on either end of a three-hour ferry ride across the Gulf of Maine.

Across the gulf

That this genetic “whodunit” ever started amazes parents of Alstrom children. They long thought their problems would continue as a footnote in medical and scientific journals more interested in problems affecting larger populations.

Sandra and Leland Surette of Belleville, Nova Scotia, outside of Yarmouth, learned in 1990 that their newborn baby daughter, Cheryl, had the disorder. Both parents carried the recessive gene that made it possible.

“I had been told, ‘Well, Mrs. Surette, you’ll never see research into this. It’s too rare,'” Sandra says.

Then, in 1995, she got a call from Marshall, who said her laboratory was researching Alstrom. “I just about hit the couch,” says Sandra recently over lunch at a Chinese restaurant in Yarmouth.

Today Marshall plays referee on an Internet list serve where teen-agers with Alstrom trade ideas free from the prying eyes of their parents. Many of the Alstrom children who have been part of the laboratory’s research e-mail Marshall directly, including Cheryl, now 12.

While Cheryl knows a lot about the disease that is stealing her eyesight and hearing, as well as making her obese and diabetic, she doesn’t like to talk about it much. But it’s always there, lurking in the recesses of her consciousness.

It’s late afternoon at the Surettes’ two-story house on the shore of Eel Lake, and Cheryl has been in her room for some time. She comes down with her doll Jean and addresses her parents and visitors who’ve been at the house for hours.

“Jean’s hearing, speaking and vision has returned,” she says, clutching the doll. “She was in a dream and there was a guy who made her speak and hear and see all over again.”

Cheryl, an only child, long has been told she’s “special.” She wears glasses with wine-red lenses to shield her sensitive eyes from the light, is slightly chubby, and is developmentally delayed in some ways. She loves to read and readily flashes a bright smile.

It’s a miserable day. The steady drizzle has made the family dog a dripping mop as she paces outside her doghouse. The black flies are biting near the lake and the ground is sodden.

Cheryl is fresh off the school bus after a day at public school, where she’s fortunate to have a full-time teacher’s aide paid for by the government.

At school, she’s made a detailed drawing of traffic lights designed to her own specifications, which she now shows off in the kitchen to her parents and a reporter and photographer.

A brown light is for “no bad people,” she says. “That’s if terrorists were coming, that light would be on.”

During the afternoon, Cheryl, who speaks French and English equally well, displays her knowledge of the solar system, public television’s Teletubbies, and her favorite actor, Whoopi Goldberg.

Goldberg’s first idea for a stage name was “Whoopie Cushion,” but her mother didn’t think that respectable, says Cheryl. It’s one of Cheryl’s dreams to meet Goldberg, and Sandra and Leland have put in a request to the Make-A-Wish Foundation.

Cheryl is going blind. She still can read, using a machine that magnifies text 20 times, but she also is learning Braille. With hearing aids, she still hears well. And while Sandra says she prays for something that will help Cheryl by at least halting the progression of Alstrom, both parents know the road will be long.

Earlier in the day, Sandra went to pick up Cheryl at the bus stop and Leland, who is assistant manager of an ambulance service, reflected on the seemingly inevitable deterioration that his daughter will endure.

“It’s something that’s back there, that you know eventually that door is going to open,” he says. “Sometimes we can be quite discouraged, [but] you just swallow and go on.”

Memories of three daughters

The next day it’s raining again. About 20 minutes from Yarmouth is Surette’s Island, where Leland Surette grew up. It is connected to the mainland by a single-lane iron bridge that was considered to be an engineering marvel in the early 20th century when it was floated into position. The bridge may have joined the island to the mainland, but it could not overcome the isolation that Leland’s distant cousins Roy and Victorine Muise felt in the 1940s when three of their nine children were born with an unknown disorder that progressively caused blindness, obesity and other problems.

In 1995, when Jan Marshall heard about the Muises’ three girls, all of whom were dead by then, she made the trip across the iron bridge with her own 13-year-old daughter to learn more. She was visiting a couple who only recently had learned that their daughters had died of Alstrom syndrome.

Victorine, now 76, recalls Marshall saying, “You know more than we do about Alstrom’s.”

The meeting with Victorine yielded valuable information for the Jackson researchers.

“She described quite thoroughly a lot more than we knew about the progression of the disease,” remembers Marshall.

In 1946, Victorine gave birth at home to a girl named Patsy. At first everything seemed fine, but when she put Patsy into a carriage and brought her into the sunlight, the baby screamed and screamed, she recalled. It was the sensitivity to light.

In 1949 Bertha was born, and Esther was born in 1954 – still five years before a Swedish scientist named Carl Henry Alstrom published a paper on the genetic disorder. Both Bertha and Esther lived to be 24 years old. Patsy lived to the age of 40.

Victorine remembers telling Marshall “the real story – how hard it was.”

Doctors had little to offer. There were a few Braille sessions available after a trip, which helped two of the daughters, but public support was almost unknown. While Victorine didn’t have trouble dealing with her daughters’ blindness on an island with more lobster traps than people, the serious illnesses that came late in their lives were deeply trying, she said.

To this day, Victorine admits she’s still confused about the nature of the genetic disorder. Why did three children have it and not the other six?

The reason is that Alstrom syndrome is a hereditary, recessive disorder. A person who has it must have inherited two copies of the mutated gene, one from each parent.

Parents who don’t have Alstrom but who can pass the disorder on carry just one copy of the gene. The probability of two parents each having the mutated gene giving birth to an Alstrom child is about one in four.

None of the Muises’ seven grandchildren has Alstrom syndrome.

Now, almost 20 years since Patsy died, Roy, a retired lobsterman, and Victorine speak matter-of-factly about their three daughters. Victorine remains fascinated by some of the skills her children had. Patsy, for instance, could “count money, oh my, she could count [paper money] faster than I can, and I can see,” she says.

By touch, Patsy could tell the denomination of each bill. Patsy also could pick out matching clothes from a pile without fail, Victorine said.

Roy fights back his emotions as he brings out a framed, graying photograph of the three girls. Bertha is standing in the middle, smiling broadly for the camera.

Hope for the future

Victorine hopes Jackson Lab’s genetic discovery soon will allow parents to get tested to learn whether they could give birth to an Alstrom child. Such testing is possible, but it hasn’t happened yet at clinical sites.

Sandra Surette worries about the implications of testing. She says she thinks parents who may carry the gene should make their own decisions about whether to undergo genetic tests to determine if they carry the recessive genes that can combine to create Alstrom.

“I think what I would say to any couple thinking of the test is you have to hear my side of the story as well,” Sandra says.

“My gosh, I wouldn’t trade Cheryl in for the world.”

Jan Marshall points out that testing won’t be something The Jackson Laboratory, a research facility, will be doing.

Scientists there are working on creating a mouse with the Alstrom disorder. That may be accomplished in as little as a year. The mouse mutant will serve as a model for scientific study to find out how the gene functions.

While major discoveries may not come in time for people like Cheryl Surette, the hope is that research may lead to drugs or treatments to prevent Alstrom syndrome or lessen its symptoms.

Anyone interested in more information or making a donation should write Alstrom Syndrome International, 14 Whitney Farm Road, Mount Desert, ME 04660.