Researchers from the Weizmann Institute of Science in Rehovot and the Hadassah Hospital in Jerusalem have identified the gene whose defective versions cause the development of a unique muscular dystrophy
From right to left: Dr. Edna Ben-Asher, Dr. Tzvia Olander and Dr. Nili Avidan. Genetic roots
Researchers from the Weizmann Institute of Science in Rehovot and the Hadassah Hospital in Jerusalem have identified the gene whose defective versions cause the development of a unique muscular dystrophy (HIBM type hereditary myopathy). This disease is common among Jews from Iran and its neighboring countries. The discovery was recently published in the journal Nature Genetics. The first description of this disease was recorded for the first time in 1984 by Prof. Zohar Argov from the neurology department at the Hadassah Ein-Kerem Hospital in Jerusalem. The disease manifests itself in gradual muscle weakness in the legs, and at a later stage affects the muscles of the hands and leads to general disability. In 1996, the genomic location of the gene responsible for the disease was mapped: the short arm of chromosome nine.
This discovery, by Prof. Stella Mitrani-Rosenbaum from the Molecular Biology Unit at Hadassah Mount Scopus Hospital, was the beginning of the deciphering of this unique muscular dystrophy. From this stage another five-year effort was required, which ultimately resulted in cracking the riddle of the difficult disease. In this genetic pursuit, researchers from the Crown Center for the Study of the Human Genome at the Weizmann Institute of Science played a central role. Prof. Doron Lantz, Prof. Jackie Beckman, Dr. Edna Ben-Asher, Dr. Nili Avidan, Dr. Tzvia Olander, and Dr. Miriam Chen participated in this team. Working together with you were Prof. Stella Mitrani-Rosenbaum, her research students, Iris Eisenberg and Hagit Hochner, as well as Dr. Tamara Potikhat, Mark Barash, Moshe Shemesh, Gil Grabov, Ina Shmilewitz and Prof. Adam Friedman from the Department of Molecular Biology at the Hadassah Mount Scopus Hospital .
The scientists used the databases created as part of the Human Genome Project in a sophisticated manner, and thus, together with their colleagues from the Hadassah Hospital, they were able to identify the genetic transformation (mutation) that causes the disease. The discovered mutation damages an enzyme that plays a central role in the pathway responsible for building sialicacid type sugar fragments (molecules) which are an essential component in the structure and function of many proteins. The researchers hypothesize that the lack of sugar causes the accumulation of damaged protein in the muscle cells, which causes their degeneration. This discovery will open an opening for a better future understanding of muscular dystrophy, and at a later stage even for the development of advanced measures to cure the disease. A genetic test that was already developed following the discovery now enables prenatal diagnosis for families from the risk population. This is especially important for Jews of Iranian origin, among whom one in 20 people carries the mutation. The researchers point out that the mobilization of the families of the patients in Israel and abroad for the overall effort to assist in the research, both by providing blood samples and by their generous financial support, was decisive in its importance and contribution to deciphering the genetic basis of The research was carried out as part of the National Laboratory for Genomic Infrastructure, which operates at the Weizmann Institute of Science with the support of the Ministry of Science.
