A team of researchers from Ben-Gurion University of the Negev has deciphered a genetic disease common among Jews of Moroccan ancestry that can cause severe mental retardation and epilepsy. Then, brain atrophy emerges and they begin deteriorating, reaching severe retardation by one year of age, with enhanced muscle tone and epilepsy in most cases. The disease, which the researchers have called PCCA2 (progressive cerebello-cerebral atrophy type 2), was shown to be caused by mutations in the gene VPS53. Two mutations were found in this gene, and both are common in Jews of Moroccan ancestry (one of every 37 Moroccan Jews carries one of the two mutations). The researchers, led by Professor Ohad Birk, head of the Genetics Institute at Soroka University Medical Center and the Morris Kahn Lab at the National Institute for Biotechnology in the Negev at Ben-Gurion University, showed that the VPS53 mutations cause defective circulation of vacuoles (endosomes) within patents' cells, leading to detrimental excessive storage of "junk" within the cells. PCCA2 is a recessive disease: If both parents are carriers of a VPS53 mutation, there is a 25% risk of the disease in each pregnancy. Based on the high carrier rate, PCCA2 marks the most common severe genetic disease in Moroccan Jews discovered thus far. In 2010, Birk's group discovered another gene for a similar disease, PCCA, which is common in Jews of Moroccan and Iraqi ancestry (1:40 carrier rate in both cohorts). Unlike PCCA2, in PCCA the disease mechanism is totally different. The mutations in PCCA are in a different gene, SESPSECS, abrogating the body's ability to utilize the essential micronutrient selenium. Based on these studies, routine government-funded free carrier testing for SESPSECS mutations has been introduced in Israel in 2011 for all Jews of Moroccan or Iraqi ancestry. PCCA and PCCA2 are the two most common genetic diseases in Jews of Moroccan Jews, and have never been described before worldwide. Deciphering the genetic and molecular mechanism of disease enables their prevention. Routine carrier testing for this disease in Moroccan Jews will likely ensue within months. Carrier testing and prenatal diagnosis of PCCA will enable eradication of this severe disease, as has previously been done for other common genetic disease in Jews, such as Tay-Sachs.
