Researchers at Haifa's Rambam Medical Center and the Technion's medical school have for the first time identified a rare syndrome - among five of 11 children born to Israeli Arab first cousins who married - that combines baldness, mental retardation and neurological problems that make walking difficult. Their description, just published in the American Journal of Human Genetics, has implications for understanding cell metabolism in humans, as the lack of a certain protein in the victims also plays a crucial role in the assembly of ribosomes, "factories" for protein synthesis found in every cell of the body. Thus, the study of this syndrome and other rare inherited disorders offers unique opportunities for insight into basic biological processes of potential relevance to extremely common human diseases. Prof. Eli Sprecher of Rambam's molecular dermatology laboratory and of the Technion-Israel Institute of Technology's Rappaport Faculty of Medicine Center for Translational Genetics, along with doctoral student Janna Nousbeck, learned of the family members when they were referred by Emek Medical Center in Afula. The researchers dubbed the extremely rare, complex disease ANE Syndrome due to the absence of hair (alopecia), neurological defects and hormonal deficiencies (endocrinopathy). Using a wide variety of advanced technologies, Nousbeck and co-workers managed to demonstrate that ANE Syndrome results from a defective recessive gene that causes the absence of a small molecule called RBM28. With the help of a Japanese collaborator, Dr. Akemi Ishida-Yamamoto, they discovered that the missing molecule in ANE Syndrome plays a crucial role in the assembly of ribosomes. The story began about two years ago when members of the large family were referred for genetic counseling to Drs. Ronen Spiegel and Stavit Shalev at Emek Medical Center. The symptoms are varied in the five patients, who all live at home and are mainly taken care of by the elderly father. One has no hair on his body at all, while one has hair on his head but not on his body, including the armpits; two others have completely bald heads. The protein's absence also affects the adrenal and pituitary glands and the production of sex hormones. The Rambam research team head said the family regards its affliction as fate, but that they did fully cooperate with the scientists. By studying the disorder, the research team identified the cause of the new disease, allowing for proper genetic counseling for the family. Sprecher said the symptomless children may be carriers and thus will require genetic counseling to ensure that they don't marry a fellow carrier in the closed, isolated community; if they already married, they would need a prenatal diagnosis to avoid having a child with the syndrome. Ddeciphering the disease's molecular basis is in itself important, as the team went further, investigating the underpinning of the role played by RBM28 during tissue development and shedding new light upon a very fundamental biological process. Sprecher said their discovery "constitutes a breakthrough in our understanding of cell biology" and is part of their long-standing effort over the past decade, which has led so far to the elucidation of the cause of no fewer than nine genetic diseases, including five new ones. Sprecher said it is not very likely the difficult-to-diagnose syndrome exists in other places, as the the genetic mutation was cultivated within the extended family, which has inbred. However, he said he is eager to hear from doctors and researchers in other parts of the world who have noticed a similar combination of dermatological, neurological and endocrinological symptoms in patients. "As Israel offers modern Western medicine and includes closed populations that inbreed, the syndrome was noticed and identified. In a closed, non-Western society, it would not be." After investing two years of research in the project, the Rambam-led team is now learning about the role of the gene in the functioning of ribosomes and what the missing protein does. "Maybe we could intervene in what causes the non-functioning of ribosomes. When the protein does not exist, ribosomes are not constructed properly. We know the protein is important in creating another protein that controls hair growth," Sprecher said.