From the Packard Center for ALS Research:

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.