A team of researchers from the Hadassah Medical Organization and the Weizmann Institute of Science has uncovered a gene causing Mucolipidosis IV (ML4), a rare hereditary disorder characterized by severe mental and motor retardation as well as vision abnormalities. This is one of the few cases in which a team composed entirely of Israeli scientists has discovered a gene for a genetic disease. Their findings will appear in the September issue of Nature Genetics.
Ashkenazi Jews account for over 80% of the mucolipidosis patients worldwide. First described in 1974 by a team of Hadassah physicians and scientist, ML4 is caused by a genetically induced biochemical disorder leading to impaired fat breakdown. Prof. Gideon Bach of the Hadassah Genetics Department has studied the disease since 1975.
Having pinpointed the potential disease-causing region to a narrow stretch on chromosome 19, Ruth Bargal of Prof. Bachs laboratory paired up with scientists at the Weizmann Institute Crown Human Genome Center, headed by Prof. Doron Lancet. The team, which included Drs. Edna Ben-Asher, Nili Avidan, and Zvia Olender, identified the mucolipidosis gene and determined its DNA sequence.
The newly discovered gene has telltale signs indicating an involvement in lipid breakdown. This is in line with the presumed metabolic origin of the disorder, and may explain why patients show an accumulation of fats and sugars in their lysosomes -- membrane bound intracellular sacs that function in food digestion.
Most importantly, the collaborative team has found several specific mutations that cause the disease in different groups of patients. ML4 is recessive, meaning that the disease may appear if both parents carry a mutated gene. Since the researchers revealed the mutations accounting for 95% of all disease cases in Ashkenazi Jews, their findings will now enable effective population screening for detecting carriers, and accurate prenatal testing for fami
Contact: Jeffrey J. Sussman
American Committee for the Weizmann Institute of Science