Human Gene, Cause of Rare Disease, Found

Date: April 2002

World famous for genetic research using mice as models for human disease, The Jackson Laboratory has announced the discovery of a previously unidentified human gene. This marks the first human gene discovered at the Bar Harbor institution. Mutations in this gene, ALMS1, causes Alström syndrome, a very rare condition that affects some170 people. But its discovery may open pathways for understanding common human conditions including obesity and diabetes.

"Obesity is one of the critical health issues of our time," explained Jürgen K. Naggert, Ph.D., a member of the research team. "This discovery provides researchers with another insight and entry point into understanding obesity."

Ten years ago, Jackson Laboratory Staff Scientists Drs. Naggert andPatsy M. Nishina noticed that, like one of their mouse models, children with this genetic condition become blind, obese, hearing impaired and diabetic. Vision loss begins in infancy and often is the first symptom.  Most sufferers lose their sight during early childhood. By testing DNA samples of patients with Alström syndrome and comparing them to samples from the general human population, the scientists isolated a gene, ALMS1, which is mutated in the Alström patients. 

The function of the protein encoded by ALMS1  remains unclear. " The gene is expressed in all the organs that exhibit symptoms," explained Dr. Nishina,  "indicating that the disease is caused by the malfunction of the protein in those individual organs."

To develop the syndrome, which affects both boys and girls, a child must inherit an allele? mutated gene?from both parents. An adult with one copy of the mutated gene has no detectable symptoms. Statistically, if two adults each have one mutated gene, there is a 1-in-4 likelihood that a child of this couple will inherit the two alleles required to develop the syndrome.

Discovery of the ALMS1 gene may hold promise for investigations into other more common diseases in the general population. One value of studying this gene lies in the access it may provide to novel metabolic and regulatory pathways involved in obesity, type 2 diabetes, neurosensory diseases and related disorders. Determining the function 

of the ALMS1 gene will potentially provide insights into how this gene interacts with other genes to produce its pathological effects. 

The research team is now developing a mouse model of the disease for further research.

The research is published in the May 2002, issue of Nature Genetics. The paper will be published online on the Nature Genetics website as of Monday, April 8: go to
http://www.nature.com/cgi-taf/dynapage.taf?file=/ng/journal/vaop/ncurrent/index.html.

More information about Alström syndrome, including links to other resources, is available on The Jackson Laboratory's website: www.alstrom.org.

Collin, GB, Marshall, JD, Ikeda A, So WV, Russell-Eggitt I, Maffei P, Beck S, Boerkoel CF, Sicolo N, Martin M, Nishina PM, Naggert JK. Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome. Nature Genetics, May 2002, Volume 31.
 

Contact(s): Joyce Peterson, 207-288-6058, joyce@jax.org

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