A genetic disease common among Jews of Moroccan origin has been deciphered

A research team led by Prof. Ohad Birak, Director of the Genetics Institute at the Soroka Medical Center and head of a laboratory at the National Institute of Biotechnology in the Negev at Ben-Gurion University, deciphered a genetic disease that causes cases of severe mental retardation and epilepsy among Jews of Moroccan origin

A research team led by Prof. Ohad Birak, Director of the Genetics Institute at the Soroka Medical Center and head of the Maurice Kahn Laboratory at the National Institute of Biotechnology in the Negev at Ben-Gurion University, deciphered a genetic disease that causes cases of severe mental retardation and epilepsy among Jews of Moroccan origin.

The research was carried out as part of Miora Feinstein's doctoral thesis in the laboratory of Prof. Birak, and was attended by Dr. Hagit Flosser, Prof. Baruria Ben Zeev, Prof. Tali Shagia, Dr. Dorit Lev, Dr. Orli Agami as well as other students from the research laboratory. The research, published these days in the scientific journal Journal of Medical Genetics, was funded by the National Science Foundation (ISF), a licensed foundation and Teva.

This is a disease in which apparently healthy children are born, but in their first year of life, a developmental setback begins and by the age of two, severe mental retardation is manifested, followed by muscle stiffness and epileptic seizures.

The disease, which the researchers named PCCA2 (Progressive Cerebello Cerebral Atrophy type 2), is caused by mutations in the VPS53 gene. In this gene, the two most common mutations among Jews of Moroccan origin were found - one out of every 37 Jews of Moroccan origin is a carrier of a mutation in this gene.
The researchers showed that the mutations in the gene cause a defect in the transport of substances inside the cell, and as a result, excessive and harmful storage of substances inside particles in the cell called endosomes. The inheritance of the disease is recessive, meaning that only if both spouses carry the mutation in the gene, there is a 25% risk of the disease in each of their offspring.

In light of the high prevalence of the carriers of this new disease, a screening test for this disease will probably be integrated in the future as part of the genetic tests routinely offered to expatriates of Moroccan Jewry before pregnancy.

In 2010, Prof. Birak's research group published a gene for a similar disease - PCCA, which is more common in Jewish children from Morocco and Iraq (1:40 in this population is a carrier of the disease).
The mechanism of PCCA disease is completely different from that of PCCA2 disease. PCCA disease involves mutations in the SEPSECS gene that cause a deficiency in the body's ability to use selenium - a dietary component that is absorbed by the body in minute but critical amounts. Due to the prevalence of the disease among Jews from Morocco and Iraq, from 2011 the Ministry of Health introduced screening tests for carriers of the PCCA disease, as free tests for this population.

PCCA disease and PCCA2 disease, the two most common severe genetic diseases among Moroccans, have not been described at all in the past and deciphering their genetic basis and biochemical mechanism allows their prevention.

Prof. Birak's research team has so far deciphered more than twenty of the most common genetic diseases in the Arab-Bedouin world and among non-Ashkenazi Jews. Beyond the great scientific interest, the results of the studies are immediately applied in genetic screening tests for massive prevention of these serious diseases in Israel and around the world.

• The full research findings published in the scientific journal Journal of Medical Genetics