The Extremely Rare Disease BPTA Syndrome may Lead Scientists to Prevent the Development of Cancer


The Schleswig-Holstein University Hospital and the Max Planck Institute in Germany have investigated a hereditary condition that is extremely rare called brachyphalangy, polydactyly, and tibial aplasia/hypoplasia (BPTA) syndrome. Symptoms of BPTA syndrome include but are not limited to, malformation of extremities, nervous system, and face.

According to a recent article in News Medical & Life Science, during the study, the team worked with hundreds of genetic changes that were associated with such conditions as abnormal brain development and increased cancer risk.

A Change in the Charge

It is believed that BPTA is caused by a change in the charge of a protein that disrupts cellular self-organization, a process whereby interacting cells opt for a higher order of patterns.

A change in the charge causes HMGB1 to resemble proteins that cluster in a small area of a cell’s nucleus and accumulate incorrectly. This leads to a disruption in the organism’s development.

Martin Mensah M.D., a fellow at Charité, is one of the first authors of the study. Dr. Mensah acknowledges the difficulty in studying these protein segments. The proteins must first carry out a series of maneuvers before producing effects.

Little is currently known about the thousands of changes relating to various diseases and conditions. Therefore, Dr. Mensah further explains, it is seldom clear how the mutations produce disease.

The presence of certain chemicals, as well as changes in pH and temperature, cause a disruption in the shape of a protein. The protein also loses its ability to function. The process is called denaturation. But first, in order for a cell to reproduce, it must carry out a series of maneuvers.

About the Frameshift Mutation

The team decoded genetic information from five out of the ten affected patients. They found that each of the five patients had changes in the HMGB1 protein. A positive charge was found in one-third of the protein’s structure due to a frameshift mutation rather than the usual negative charge.

As a result, the HMGB1 mutated protein which is incorrectly drawn to the nucleolus has developed a stiff extension and clumps together.

Henri Niskanen, M.D. also a first author, explains that examining the nucleolus under the lab’s microscope enables the researchers to observe the loss of liquid-like properties as the nucleolus becomes rigid. This has a negative effect on the cells’ functioning. Malte Spielmann, M.D., another lead author, further explained how a disease can be caused by mutations in disordered protein sections.

As a result of a change in the charge, the protein mistakenly accumulates in the nucleolus. It disrupts its functioning and leads to a malfunction in its development.

Searching the Databases

The researchers looked for cases that were similar. They located six hundred mutations in sixty-six proteins from databases containing the DNA sequences of several thousand people.

They found 101 mutations that had been connected to various diseases. This included neurodevelopmental disorders and an increase in the risk of cancer.

The cell structures of thirteen proteins were studied and half interfered with the function of the nucleolus just as with BPTA syndrome.

The Researchers Opened the Door to Other Diseases

According to Denise Horn, M.D., lead study author, the team discovered a mechanism in the BPTA syndrome that could be associated with other diseases such as cancer. Dr. Horn stated that it may be possible to prevent the development of cancer through the intervention of the cell’s self-organization.


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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