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SCIENTISTS FIND FOURTH GENE FOR INHERITED
ALS An international research team has pinpointed the gene for ALS4, now the fourth gene to be discovered for a familial variety of ALS. The rare form of the disease appears earlier than the more common sporadic form of ALS, affecting boys in their teens and women in their thirties. Also, because it doesn't injure breathing or swallowing muscles, patients with the ALS4 gene typically live a normal life span, though they may be wheelchair-bound as the disease progresses. Two Johns Hopkins neurologists who are members of The Packard Center for ALS Research, David R. Cornblath, M.D., and John W. Griffin, M.D., were part of the research team, which included scientists from the University of Washington, the NIH, Australia and Belgium. An article on the study will appear in the June issue of "The American Journal of Human Genetics." "With this information, The Packard Center can develop mouse models that will help us better understand the specific biology of this disease and of ALS in general," Cornblath explains. "In fact, Center researchers at Johns Hopkins have now begun the work that should lead to those models," says Jeffrey Rothstein, M.D., Ph.D., who directs the Packard Center. "Before long, we hope to understand the nature of the ALS4 protein. That will put us closer to finding common principles that underlie all forms of the disease." The gene in question, on human chromosome 9, was found after researchers doggedly narrowed down the specific area associated with disease. The gene is a dominant one, meaning patients see its effects even if only one parent contributes the gene. And it's carried on a non-sex chromosome, commonly called an autosome. Thus the ALS4 disorder is referred to as "autosomal dominant juvenile ALS." With the aid of families who have the disease - "and in this matter, the families were exceptionally helpful," says Cornblath - the scientists collected patients' blood samples and analyzed the DNA. The researchers found that the mutant ALS4 gene produces an abnormal version of DNA/RNA helicase, an enzyme involved in repairing damage to those two major molecules and in allowing them to reproduce and carry out their role of directing a cell's protein production. At least one other motor neuron disease, spinal muscular atrophy, may also be linked to abnormal helicases. The discovery brings to five the number of familial or inherited varieties of ALS. ALS1 is also the result of an autosomal dominant gene, but one that brings about an aggressive disease in adults. The gene codes for an abnormal form of an enzyme called superoxide dismutase. ALS2 is caused by a recessive gene on chromosome 33 and has its typical onset at age twelve. ALS3 is linked to chromosome 18 and strikes in adulthood. ALS5 is due to a recessive gene on chromosome 15. |
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