A research team headed by Prof. 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 BGU has unraveled the genetic basis of a hereditary disease causing severe mental retardation and epilepsy in Jews of Moroccan ancestry.
Affected children are seemingly fine at birth and develop well until about six months of age. 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 Birk group 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 is the most common severe genetic disease in Moroccan Jews discovered to date, and 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.
It should be noted that in 2010, Prof. 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.
The research was done as part of the doctoral thesis of Miora Feinstein in Prof. Birk's lab. Dr. Hagit Flusser, Prof. Bruria Ben-Zeev, Prof. Tally Lerman-Sagie and Dr. Dorit Lev contributed to the clinical aspects, and Dr. Agamy and others of the Birk lab took part in the molecular studies. The study, published this week online in the Journal of Medical Genetics was financed by the Israel Science Foundation (ISF) and the Legacy Heritage fund.
Prof. Ohad Birk conducts groundbreaking genetic research through the Naomi Fisher Bartnoff Genetic Counseling Unit at the Dayan Clinical Wing of Soroka University Medical Center, and the Morris Kahn Lab of Human Genetics of the NIBN at BGU. His research has led to the discovery of more than 20 genetic diseases common in Arabs and in Sephardic Jews, providing insights into the nature of illness and unraveling molecular pathways of normal human development. His translational approach has led to dozens of routine massive genetic carrier tests, prevention and practical eradication of numerous severe neurological disorders common in Arabs and in Sephardic / non-Ashkenazi Jews.