New mutations have been found in the genes responsible for two serious neurological diseases that have not been described to date

The journal NEURON publishes a study jointly led by Israeli and American researchers

In a research collaboration between the Sheba Medical Center (Prof. Boruria Ben Ze'ev, Director of the Pediatric Neurology Unit, Prof. Yair Anixter, Director of the Metabolic Diseases Unit at Edmond and Lili Safra Children's Hospital and Prof. Alon Peres, Head of the Genetic Institute), the Weizmann Institute of Science (Prof. Doron Lantz, Head of the Crown Center for Genome Research) and Duke University in North Carolina (Prof. David Goldstein, Head of the Center for Diversity Research the genome), new mutations were found in two genes responsible for two different serious neurological diseases, manifested in infancy and early childhood. The goal of the overall research project is to locate the genetic cause of a hundred severe genetic diseases in the Israeli population, the cause of which has so far been unclear despite extensive investigation processes.

Changes in the first gene cause a rare type of microcephaly (small brain) that is found in children of Iranian Jewish origin who have been monitored for years in the pediatric neurology unit at Edmond and Lily Safra Children's Hospital as well as in the pediatric neurology unit at Wolfson Hospital. The symptoms of the disease are a small head circumference at birth and delay in head growth afterwards, deep retardation and convulsions. The disease causes severe disability throughout life and affects both boys and girls.

The new study revealed that the gene defective in the disease is the gene encoding the protein enzyme ASNS (ASPARAGINE SYNTHETASE) responsible for the creation of the amino acid asparagine. This substance, one of the twenty building blocks of all proteins, is indeed supplied from dietary sources, but apparently in the presence of the genetic defect there is a significant decrease in its concentration in the brain, which impairs brain development from early stages and cumulative damage even after birth. It is important to note that although this is a "metabolic" disease, the usual metabolic tests do not detect the deficiency because the measured values ​​do not deviate significantly from the norm, therefore the possibility that has now been opened for a specific genetic test is important. The prevalence of pregnancy in Jews of Iranian origin is high and reaches 1:60. The discovery of the gene will allow the identification of carriers of the disease before and during pregnancy, and the diagnosis of additional patients.
Also, the possibility of therapeutic intervention in cases that are not diagnosed in the prenatal stage is now being examined at the research level. This discovery was widely published this week in the prestigious scientific journal NEURON.

In another study within the framework of the Israeli-American project, another genetic disease was deciphered among children of Bukhari origin, who were treated in the pediatric neurology unit at Safra Hospital. This disease is also a severe neurological disease that includes developmental delay, muscle disorder, when a significant number of children do not develop independent walking, epilepsy is sometimes detected in them, their height is short and there are breathing disorders in them that require night breathing, to the point of needing continuous breathing. This genetic disease results from a destructive mutation in the gene called TECPR2 which is involved in the breakdown of waste materials in the various body cells, including the brain, in a process known as AUTOPHAGY, which has been researched for many years by another research partner from the Weizmann Institute of Science - Prof. Zebulon Elazar. There is currently no new knowledge regarding specific treatment options for the disease and no diseases similar to it have been described in the literature to date, especially in reference to the respiratory disorder. In this case too, a high sectarian prevalence was found: among Bukhari Jews, the prevalence of the mutation is about 1:40.

The importance of identifying the gene is for the purpose of early identification of carriers that will enable the prevention of the birth of sick children, as a basis for research to understand the unique mechanism of the genetic defect at the cellular and neurological level, as well as to understand the importance of the gene in the regulation of the respiratory system. The genetic finding was recently published in the important newspaper AMERICAN JOURNAL OF HUMAN GENETICS.

The identification of the two new genes is the result of a collaboration between clinicians who correctly define the picture of the disease in the various patients, geneticists who apply the newest methods to locate the responsible genes, and researchers in basic science who delve into the mechanisms of action of the various proteins that are damaged as a result of the genetic defect.

These collaborations between factors in Israel and around the world enable the prevention of the appearance of serious genetic diseases in populations at risk, but should also lead to the understanding and development of tools in the future for the treatment of these and similar diseases