Genetic find

By Judy Siegel-Itzkovich

Hereditary inclusion body myopathy (HIBM), an incurable disease which causes progressive muscle degeneration, is most common among Jews of Persian (Iranian) origin. The disease usually presents symptoms when a patient (who inherited it from two "carrier" parents) is in his or her 20s, and is characterized by various degrees of progressive muscle weakness first in the legs and later in the arms, eventually leading to general disability and even total paralysis of the voluntary muscles.

Researchers at Jerusalem's Hadassah Hospital, in collaboration with colleagues from the Weizmann Institute of Science in Rehovot, have recently identified the gene, which in a mutated form causes HIBM. This discovery will benefit not only the future children of individuals who carry the mutant gene but could also help people who suffer from different types of muscle-and neuro-degenerative diseases.

The most common form of HIBM was first described in 1984 by Prof. Zohar Argov of the Hebrew University - Hadassah Medical School neurology department. 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 on chromosome nine. Carried by an estimated 5-10 percent of Jews of Persian origin, the relatively high incidence of HIBM is due to the intermarriage rate among members of this community. (The study of genetic diseases has often focused on Jews of various origins because of their widespread preference of marrying within their own circles over many centuries.) The researchers have developed a blood test to detect the mutation, which is already available at Hadassah's Mount Scopus hospital as part of pre-natal genetic counseling for high-risk couples, especially those of Persian origin.

The team, led by Hadassah's Professor Stella Mitrani-Rosenbaum, made use of the databases created within the framework of the international Human Genome Project. The gene was also detected in Jews from Egypt, Afghanistan, Iraq and among Karaites (a Jewish sect dating back to the eighth century). A different form of the mutated gene has been found to cause a small number of HIBM cases in an Israeli Bedouin family, among black and white persons in the US state of Georgia, and among residents of the Bahamas, eastern India, Denmark and Italy. Their research was recently published in the prestigious US journal Nature Genetics.

The research was conducted under the aegis of the National Laboratory for Genome Infrastructure at the Weizmann Institute, and supported by the Ministry of Science, Culture and Sport. Affected families in Israel and abroad provided blood samples as well as some of the financial backing for the study.

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. A lack of sialic acid leads to accumulation of defective proteins in muscle cells, thus causing muscle degeneration. Argov believes that the gene discovery could facilitate the understanding of other genetically transmitted degenerative muscle diseases - including distal myopathy as well as diseases that are caused by a "degenerative cascade" leading to apoptosis (cell death), such as Alzheimer's.