The New England Journal of Medicine reports that a multinational team, spearheaded by medical geneticists at Jerusalem’s Shaare Zedek Medical Center, has discovered a gene responsible for a serious inherited disorder.  The disorder is “polyarteritis nodosa” (PAN), a form of vasculitis (disorders that destroy blood vessels by inflammation) and can also cause damage to the immune system.   PAN is caused by adenosine deaminase (ADA2) deficiency and in some cases is fatal.

The discovery was made when doctors recognized symptoms in the children of Jews of Georgian (Caucasus, former Soviet Union) origin.  At least one in 100 couples of Georgian origin are both carriers of the disease, and since there are at least 100,000 Israelis of Georgian origin there would be some 200 cases here alone, said Prof. Ephrat Levy-Lahad, Director of the Fuld Department of Medical Genetics at Shaare Zedek, who led and coordinated the international team over several years.  The disorder is also found among Arabs and non-Jewish residents of Germany and Turkey as well.

Describing the research, Prof. Levy-Lahad explained, “We tried to look for other families with the same disease and other ethnicities with mutations in the same place in their genome.” Some of the children with PAN “even had strokes, along with skin ulcers, rashes and neurological problems with peripheral nerve damage.”

Prof. Levy-Lahad also observed that mutations in this gene are “particularly common” in Georgian Jews, “but since not many patients are known, we presume that they are not being diagnosed.”

As a result of the team’s discovery, families found with the mutation will be referred for genetic counseling.  It is possible to perform genetic diagnosis to select unaffected, healthy embryos to be implanted for a pregnancy.

Dr. Paulina Navon-Elkan, who headed Shaare Zedek’s pediatric rheumatology clinic for many years but is now semi-retired, was involved in the early stages of the research.  She said that treatment until now included cytotoxic drugs ordinarily used for cancers, that are very aggressive.  “But now that we understand the disease’s genetic origin, we have more options.”

Prof. Mary-Claire King, the eminent geneticist at the University of Washington who was the first to identify a breast cancer mutation (BRCA1) and who sequenced genes to help Shaare Zedek and Prof. Levy-Lahad with its research to discover the gene that predisposes Ashkenazi Jews to breast cancer, commented, “This is lovely and important work and a real coup for Israeli genetics. It was a great pleasure to be a small part of it.”