Lupus gene found in Bermuda family
A doctor from one of the world’s leading universities has discovered a gene mutation in a Bermudian mother and daughter that could help to find a cure for a potential killer disease.
The two women both suffer from lupus, which attacks the immune system, causes kidneys to fail and can be fatal.
Naoka Murakami said: “It’s a unique opportunity for us and the patients in Bermuda. If we could extend this type of research in Bermuda and get more families, that would be very interesting.
“If we identify a specific mutation and the function of the gene, it gives us the potential to develop a diagnostic measure.
“It could lead to a cure for lupus — the lupus that is associated with this gene mutation.”
Dr Murakami has now launched a research project to determine if genes do play a part in the development of lupus, which was not thought to be a genetic disorder.
Dr Murakami, a research fellow who treats kidney patients at Brigham and Women’s Hospital in Boston, Massachusetts, has since found two other families on the island where more than one member has lupus. She believes there might be a genetic cause for other Bermudians with lupus as well.
She has asked them to take part in the study and give a sample of blood so their genes can be mapped by a Harvard research team.
She is also looking for funding for a major research project.
Dr Murakami said: “It’s very exciting. I hope things will move forward with the funding help and patient help.
She told The Royal Gazette that past studies on lupus had never shown a genetic association for the disease, which was what made this case so interesting.
She said: “Almost all lupus cases happen sporadically without any family history. Bermuda is a small island and has sort of an isolated population.
“I’d say the gene mutation development is nothing to do with the small size of Bermuda’s population but it might be easier to track or pick up mutations in a relatively isolated area with a small population, such as Bermuda.”
Anil Chandraker, medical director of kidney and pancreatic transplantation at Brigham and Women’s, who is also involved in the research, said the gene-mapping could be used in relation to other diseases.
He added: “We want to do this for lots of other diseases in Bermuda. It’s a really novel approach because it’s such a relatively small population.”
Dr Murakami said her interest in the mother and daughter sufferers was sparked when they both attended a clinic at Brigham and Women’s.
She added: “In this case, the daughter developed lupus at the age of ten.
“She went into kidney failure from lupus at the age of 14 and her mother at the age of about 38. They were both transplanted at Brigham in the late 1990s and both have been doing quite well over the past 20 years.”
Dr Murakami said: “One day they came to the appointment together. It was like ‘oh wow, we are seeing both together’ because it’s so rare to have the familial lupus. We asked them if there was anyone else in the family with lupus.”
The doctor said the mother told her that her late mother also suffered from lupus.
Dr Murakami said: “For lupus, it’s actually quite rare to have this type of family history. We thought this is very precious and a rare opportunity to look into any genetic cases that could be carried over generation to generation.”
The mother and daughter agreed to participate in a study to map their genes.
Dr Murakami said: “Because of the recent very rapid technological progress, we are now able to sequence every single gene to every DNA level. As humans, we carry 30,000 to 40,000 genes.
“We take advantage of whole exome sequencing. By sequencing all the genes, we know how variable this gene sequence is from the normal.
“We know how a normal sequence looks. We sequence all the genes from a patient and then match towards this normal sequence to look for any difference.
“We found one gene mutation that’s in these two affected people but also sequenced the patients’ family members who are not affected as a healthy control.
“The control people who don’t have lupus don’t have the mutation. That suggests this gene can be associated with lupus development.”
The four healthy family members had blood taken at nephrologist Wendy Outerbridge’s clinic on the island in a collaboration with kidney specialists at the King Edward VII Memorial Hospital. The Harvard researchers later sequenced and analysed their genes on a computer.
Dr Murakami appealed to Bermudian lupus sufferers, especially those with a family history of lupus, to take part in her study.
She said volunteers would not have to travel overseas and could give blood on the island.
Dr Murakami said the aim of her research was to confirm that the gene mutation already discovered in the Bermudian patients is “functionally affecting the immune system” to explore any other gene mutations that could be associated with lupus.
The researchers, who have obtained permission from an Institutional Review Board to conduct the study, will use high-tech gene editing to introduce the mutation into a healthy cell to see if it prompts a hyperactive immune reaction.
The process is costly, with sequencing for each patient costing up to $800. Ideally, the researchers would like to find 50 to 100 patients to take part.
Dr Murakami said: “If we could say this mutation is associated with lupus — and if we could confirm the mutated gene can cause the disease in experimental models — this means we’ve identified a potential therapeutic target, so we could develop therapeutic agents to activate or inhibit the function of the target gene.
“It would be a bit of a jump to say that a gene therapy could treat lupus with this specific mutation at this moment, but it is not impossible in the future.”
• Anyone interested in the study can e-mail Dr Murakami at firstname.lastname@example.org
Lupus fact file
• Lupus is a serious autoimmune disease which causes the body’s defence system to identify its own tissue as foreign and invade and attack it
• An estimated five million people worldwide have lupus, with more women sufferers than men
• The Department of Health said no statistics are collected on the number of lupus sufferers on the island
• The Bermuda Lupus Association was set up five years ago to help sufferers with information and support. The charity has about 60 members, most of whom are supporters of people with lupus
• The charity meets monthly and holds educational seminars and quarterly support group meetings. It also has a WhatsApp chat group, with about 28 members, who can ask questions about medical services, medication and offer support to each other
• The association is aware of about ten people in Bermuda who have had the disease diagnosed over the past few years. Others have lived with the disease for many years
• To get in touch with the Lupus Association, e-mail email@example.com or find them on Facebook and Instagram
• The Dragonflies youth social group provides educational and emotional support for youngsters affected by chronic illnesses, including lupus, whether as patients, family members or friends. It can be reached at firstname.lastname@example.org