The findings “open a new field of research into these common neurodegenerative diseases.”A gene prevalent in a Bedouin tribe in southern Israel that causes a severe hereditary neuro-degenerative disease has been identified by a Ben-Gurion University of the Negev research team. Children with the disease – Infantile Neuroaxonal Dystrophy (NAD) – appear to be normal until about one year of age, at which time regression ensues, reaching a fully vegetative state by the age of two years and culminating in death at 7-10 years old.
According to the chief researcher, Dr. Ohad Birk, the Israeli findings will now enable carrier detection and prenatal diagnosis for NAN both in Israeli families, as well as in many families worldwide. In addition, there are implications for treatment development for other diseases as well.
“In the long run, molecular understanding of the disease mechanism might also enable novel treatment modalities,” he said. “However, the findings have implications far beyond this disease. Iron deposition in the brain is found in ageing, as well as in severe neurodegenerative diseases in adults, such as Alzheimer and Parkinson disease. The involvement of a defect in a phospholipase enzyme in a neurodegenerative disease accompanied by iron deposition opens a new field of research into these common neurodegenerative diseases.”
Birk is an internationally known researcher from the Morris Kahn Laboratory of Human Genetics at the National Institute for Biotechnology in the Negev at BGU, and Director of the Genetics Institute at Soroka University Medical Center.
NAD is a genetic progressive disease that is found in various populations worldwide, particularly in inbred families. Brain imaging of affected individuals demonstrated diffuse cerebellar atrophy and abnormal iron deposition in discrete parts of the brain. The molecular basis of the disease was unknown and thus pre-natal diagnosis was not possible. The gene encodes a phospholipase – an enzyme which normally breaks down phospholipids. Thus, degradation of specific phospholipids in the brain of these patients is defective.
The team’s research was recently published in the American Journal of Human Genetics in parallel and independent of a similar study done by a research group in the US – studying the same disease in another population cohort. Headed by Dr. Birk, the BGU team included doctoral student Shareef Khateeb, Dr. Hagit Flusser and Dr. Rivka Ofir.
The Morris Kahn Laboratory is focused on unraveling the molecular basis of hereditary human diseases, based on studies of unique inbred communities in southern Israel. Over the past two years, the research team has unraveled eight new genes associated with human diseases (two of which have now been published) and has introduced more than two dozen novel genetic tests.
While serving the entire population of some 500,000 in southern Israel, the main focus of Birk’s work is with the nearly 140,000 Bedouin of the Negev region, who suffer a particularly high incidence of genetic disorders. According to Birk, the Bedouin community, is unique in its extreme inbreeding and consanguinity, leading to an unusually high incidence of genetic diseases.
The Negev Bedouin are a relatively isolated population, and they have a very high proportion of consanguineous marriages, with some two-thirds of individuals married to first or second cousins. As an unfortunate consequence, the Bedouin show a high rate of genetically-determined neurological, skeletal, eye, cardiac, gastro-intestinal, skin and eye diseases. There’s even “hereditary infertility” – not a contradiction in terms, explained Birk, but a matter of statistics, since if both
parents carry the defective gene, perhaps a quarter of their children will suffer the defect.
The Beduin total mutation rates are not higher than in any other population, Birk takes care to explain. “We all have mutations in our genes. But in the inbred Beduin community, individuals meet and marry carriers of the same diseases more frequently, so the rate of genetically sick infants is higher.”