Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Rare childhood bone disorder linked to gene deletion in two Navajo patients

18.07.2002

Two seemingly unrelated Native American children have one painful thing in common: juvenile Paget’s disease (JPD), an extremely rare, bone metabolism disorder. Now, researchers at Washington University School of Medicine in St. Louis and Shriners Hospitals for Children, St. Louis, have discovered that the two patients also share an unusual genetic defect. The research team found that both patients are completely missing the gene for a recently discovered protein called osteoprotegerin, known to protect bone. The study is the first to identify a genetic cause for JPD and is published in the July 18 issue of the New England Journal of Medicine.

"By identifying this genetic defect in two people, our results not only provide insight into the cause of JPD, but also shed light on the control of bone metabolism in general," says lead investigator Michael P. Whyte, M.D., professor of medicine, genetics, and pediatrics at the School of Medicine and director of the Center for Metabolic Bone Disease and Molecular Research at Shriners Hospitals for Children. "Understanding how the skeleton forms and breaks down is key to developing ways to diagnose and treat bone disorders in children and adults, including adult Paget’s disease and osteoporosis."

JPD, also known as hereditary hyperphosphatasia or hyperostosis corticalis deformans juvenilis, has only been reported in about 40 people worldwide. It is a painful skeletal disease characterized by abnormally fast formation and breakdown of bone throughout the body, resulting in debilitating fractures and deformities beginning soon after birth. These features are similar to the much more common adult disease called Paget’s disease of bone, the second most prevalent metabolic bone disorder after osteoporosis. However, JPD appears to affect all bones in the body, whereas Paget’s disease of bone involves only a select few.

The Washington University and Shriners team examined DNA samples from two Native Americans. The first was referred to St. Louis from New Mexico in 1996 for confirmation of diagnosis and treatment at one year of age. The team later learned that a second JPD patient, described in the medical literature in 1979, also was living in New Mexico. The second patient contacted the investigators and voluntarily sent her blood samples for genetic study.

The team first evaluated the gene for RANK in these two patients. In a previous collaborative study, they had identified a RANK defect as the cause of three other rare but somewhat similar genetic bone disorders also characterized by accelerated bone metabolism. The two Navajo patients, however, had normal RANK genes.

The researchers next tested the gene that makes osteoprotegerin, a protein discovered only a few years ago. Osteoprotegerin is related functionally to RANK and recent studies have found that mice lacking the protein have a condition where bone formation and breakdown is rapid, seemingly similar to osteoporosis.

The results were surprising. Neither patient had any trace of the gene for osteoprotegerin.

"At first we thought there must be something wrong with our DNA studies," says Steven Mumm, Ph.D., research assistant professor of medicine at the School of Medicine and one of the lead investigators of the study. "Instead, we realized this was a major finding."

Genetic analysis of healthy individuals confirmed the expected presence of two copies, or alleles, of the gene for osteoprotegerin. However, analysis of the JPD patients’ healthy parents revealed that each had only one copy of the gene. Furthermore, no osteoprotegerin was found in the blood of the two patients with JPD. The researchers conclude that these results provide both a cause and a mechanism for this rare bone disease, at least for these two Native Americans.

Thanks to simultaneous advances in the Human Genome Project, centered in part at Washington University, the team was able to pinpoint exactly where DNA had broken off in these two patients.

Again, the results were startling: The genetic damage was identical in both patients. The researchers therefore conclude that these two patients likely share a common ancestor, perhaps dating back a century.

"In a way, this also is a sociology story," says Whyte. "Our findings appear to represent the emergence of a "founder effect" in this population that underwent a "bottleneck" constriction years ago. The Navajo Nation decreased from about several hundred thousand individuals to about 6 thousand in the 1860s. As the population then re-grew, the missing gene apparently was passed on to their offspring. Eventually, people with only one copy of the osteoprotegerin gene married and had children with no copies of the gene."

The team now is evaluating other patients worldwide with varying forms of JPD, who so far do not appear to have any defects in the osteoprotegerin gene.

According to Whyte, this research will not only enable prenatal diagnosis for JPD in the Navajo population, but also suggests that osteoprotegerin may be a potential treatment for these affected individuals. They also expect their findings to help elucidate the role of osteoprotegerin and other key proteins in bone formation and breakdown, shedding light on Paget’s disease of bone, osteoporosis and other common metabolic bone disorders.

Gila Z. Reckess | EurekAlert

More articles from Health and Medicine:

nachricht Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>