New type of rare brittle-bone disease discovered

July 6, 2016, University of Zurich
New type of rare brittle-bone disease discovered
Credit: University of Zurich

Researchers from the University of Zurich and University Children's Hospital Zurich have discovered the first X-chromosome-inherited type of the congenital disease osteogenesis imperfecta, also known as brittle-bone disease. The new discovery improves the genetic diagnosis of the disease and paves the way to possible improved treatment options for patients.

Between 300 and 400 people in Switzerland and around half a million worldwide suffer from brittle-bone , which causes their bones to break like glass. Not only is their bone formation insufficient; other body tissues containing connective tissue are also affected. Cecilia Giunta and Marianne Rohrbach, both researchers from the Children's Research Center at the University Children's Hospital Zurich, their teams and colleagues from the USA and Thailand have now detected a new type of , identifying two families with a total of eight in all. The patients suffer from heightened bone fragility, bone deformities and stunted growth. In both families, this new form of osteogenesis imperfecta was caused by two different mutations of the same gene (MBTPS2) in the X chromosome. The disease is inherited in an X-chromosome-recessive manner and affects men and boys as only they carry a copy of the X chromosome.

Simple test in the urine

"Exactly how common the newly discovered disease is remains unclear," says Cecilia Giunta. "That said, it's easy to identify other patients, as we demonstrated that the disease can be diagnosed with a simple measurement of biomarkers in the urine." These biomarkers indicate changes in the crosslinking between the structural proteins in the bone. MBTPS2 encodes a protease, i.e. a protein, which is able to cut and therefore activate other proteins – so-called transcription factors. These activated proteins bind to the DNA and regulate genes involved in the bone and sterol metabolism and the regulation of cell stress. This was primarily shown in zebra fish in 2003. Shortly afterwards, researchers discovered that IFAP syndrome, a group of rare dermatological diseases in humans, is caused by mutations in MBTPS2.

"Surprisingly, mutations in the gene MBTPS2 also cause a completely different disease, namely osteogenesis imperfecta," explains Marianne Rohrbach. The culprit is a change in the bone metabolism, which no longer seems to be impaired in the case of dermatological diseases. Exactly how and why mutations can trigger two completely different diseases in the same gene remains unclear. The team headed by Cecilia Giunta and Marianne Rohrbach are now focusing their research on finding the answer. The scientists hope to gain new insights into developments and sterol metabolism, which could one day mean improved for patients.

Explore further: New treatment for brittle bone disease found

More information: Uschi Lindert et al. MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta, Nature Communications (2016). DOI: 10.1038/NCOMMS11920

Related Stories

New treatment for brittle bone disease found

August 9, 2013
A new treatment for children with brittle bone disease has been developed by the University of Sheffield and Sheffield Children's Hospital.

Gene discoveries give hope against 'Brittle bone' disease

May 8, 2013
(HealthDay)—Mutations in a gene involved in bone development appear to cause certain severe forms of bone loss, a finding that could lead to new therapies for the common bone-thinning disorder osteoporosis, researchers ...

Brittle bone disease: Drug research offers hope

March 31, 2015
New research at the University of Michigan offers evidence that a drug being developed to treat osteoporosis may also be useful for treating osteogenesis imperfecta or brittle bone disease, a rare but potentially debilitating ...

C-section delivery does not decrease at-birth fracture rates in infants with rare bone disease

October 22, 2015
Cesarean delivery was not associated with decrease in the at-birth fracture rates in infants with osteogenesis imperfecta, a rare bone disorder, said a consortium of researchers led by Baylor College of Medicine.

Trailblazing trial for brittle-bone disease

October 12, 2015
Foetuses burdened with a crippling form of brittle-bone disease will receive stem-cell treatment early next year in a pioneering trial, the lead researcher told AFP on Monday.

Elevated risk of death for osteogenesis imperfecta

July 5, 2016
(HealthDay)—Patients with osteogenesis imperfecta (OI) have an elevated risk of death, according to a study published online June 27 in the Journal of Bone and Mineral Research.

Recommended for you

Scientists produce human intestinal lining that re-creates living tissue inside organ-chip

February 16, 2018
Investigators have demonstrated how cells of a human intestinal lining created outside an individual's body mirror living tissue when placed inside microengineered Intestine-Chips, opening the door to personalized testing ...

Data wave hits health care

February 16, 2018
Technology used by Facebook, Google and Amazon to turn spoken language into text, recognize faces and target advertising could help doctors fight one of the deadliest infections in American hospitals.

Researcher explains how statistics, neuroscience improve anesthesiology

February 16, 2018
It's intuitive that anesthesia operates in the brain, but the standard protocol among anesthesiologists when monitoring and dosing patients during surgery is to rely on indirect signs of arousal like movement, and changes ...

Team reports progress in pursuit of sickle cell cure

February 16, 2018
Scientists have successfully used gene editing to repair 20 to 40 percent of stem and progenitor cells taken from the peripheral blood of patients with sickle cell disease, according to Rice University bioengineer Gang Bao.

Appetite-controlling molecule could prevent 'rebound' weight gain after dieting

February 15, 2018
Scientists have revealed how mice control their appetite when under stress such as cold temperatures and starvation, according to a new study by Monash University and St Vincent's Institute in Melbourne. The results shed ...

First study of radiation exposure in human gut Organ Chip device offers hope for better radioprotective drugs

February 14, 2018
Chernobyl. Three Mile Island. Fukushima. Accidents at nuclear power plants can potentially cause massive destruction and expose workers and civilians to dangerous levels of radiation that lead to cancerous genetic mutations ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.