Rehovot, Israel--Researchers from the Weizmann Institute of Science and from Hadassah University Hospital have identified the gene that in its mutated form causes a degenerative muscle disease known as hereditary inclusion body myopathy, or HIBM. This disease is common in Jews from Iran and from neighboring Middle Eastern countries, but it also occurs in non-Jews in different parts of the world. The findings are reported in the September issue of Nature Genetics.
The most common form of HIBM was first described in 1984 by Prof. Zohar Argov from the Department of Neurology of the Hebrew University-Hadassah Medical School in Jerusalem. The disease usually develops in adulthood and is characterized by progressive muscle weakness that starts in the legs but later affects the arms and leads to general disability.
Scientists began to unravel the molecular origins of the disease in 1996, when they mapped out the potential location of the gene responsible for HIBM: the short arm of chromosome 9. This discovery was made by Prof. Stella Mitrani-Rosenbaum of the Unit for Molecular Biology of Hadassah University Hospital, Mount Scopus, Jerusalem; Prof. Mitrani was later joined by graduate students Iris Eisenberg and Hagit Hochner.
However, it took five more years of intensive research to solve the HIBM puzzle. Scientists from the Crown Human Genome Center and from the Molecular Genetics Department of the Weizmann Institute of Science in Rehovot played a central role in this effort.
The Weizmann team, which included Profs. Doron Lancet and Jacques S. Beckmann, and Drs. Edna Ben Asher, Nili Avidan, Tsviya Olender and Miriam Chen, made sophisticated use of the databases created within the framework of the international Human Genome Project. Thanks to this research, scientists from the two Israeli institutions managed to identify the genetic mutations that cause HIBM. These mutations have been identified not only in people from the Middle Eastern region but also in patients from eastern India, the Bahama Islands and Georgia, United States.
The mutations affect an enzyme that plays a crucial role in the synthesis of sialic acid, a vital carbohydrate ingredient in the formation and functioning of numerous proteins. The scientists hypothesize that lack of sialic acid leads to accumulation of defective proteins in muscle cells, thus causing muscle degeneration. This discovery will facilitate the understanding of degenerative diseases of the muscle and may eventually lead to advanced methods for treating HIBM.
Based on the findings, the researchers have already developed a genetic test for prenatal diagnosis of HIBM in high-risk populations. Such genetic screening is particularly important for Jews of Persian descent, among whom one out of 10 to 20 people is believed to carry the mutated HIBM gene.
In addition to the researchers mentioned above, the scientific team that conducted the study included Drs. Tamara Potikha, Mark Barash, Moshe Shemesh, Gil Grabov-Nardini, Inna Shmilevich and Adam Friedmann of the Unit for Molecular Biology, Hadassah University Hospital, Mount Scopus, Jerusalem; Dr. Menachem Sadeh of the Wolfson Hospital, Holon, Israel; Dr. George Karpati of Montreal Neurological Institute, Montreal, Canada; and Drs. Walter G. Bradley and Lisa Baumbach of the University of Miami School of Medicine, Miami, Florida.
The researchers acknowledge the support of the affected families in Israel and abroad, who provided blood samples and generous financial backing for the study. This support was a key factor in the discovery of HIBM's genetic basis. The research was conducted under the umbrella of the Israel National Laboratory for Genome Infrastructure at the Weizmann Institute, supported by the Ministry of Science, Culture and Sport.
Prof. Doron Lancet holds the Ralph and Lois Silver Professorial Chair in Human Genomics. His research is supported by the Wolfson Family Charitable Trust, UK, Henri and Francoise Glasberg, France, The Krupp Foundation, Germany, The Kalman and Ida Wolens Foundation, Corsicanna, TX, La Fondation Raphael et Regina Levy, France, The Ernst Nathan Fund for Biomedical Research, USA, The Jean-Jacques Brunschwig Memorial Fund, The Ebner Family Biomedical Research Foundation, and the Crown Human Genome Center. His research is also funded by Mr. Abraham Goldwasser, Israel, Ms. Emilia Mosseri, Israel and Yad Hanadiv, Israel.
The Weizmann Institute of Science, in Rehovot, Israel, is one of the world's foremost centers of scientific research and graduate study. Its 2,500 scientists, students, technicians and engineers pursue basic research in the quest for knowledge and to enhance the quality of human life. New ways of fighting disease and hunger, protecting the environment and harnessing alternative sources of energy are high priorities at Weizmann.