Utilizing recently-developed genomic technology, Prof. Lina Basel, Director of Genetic Services at Schneider Children's, Genetic Services lab staff and co-researchers from the University of Ulm in Germany, have identified genes EIF2S3 and UBE3B as responsible for the development of genetic mental retardation. Research results were publicized in two leading international journals: Molecular Cell and the American Journal of Human Genetics.
The most advanced genomic methodology was applied in both research studies: whole exome sequencing, where it is possible to sequence all coded genes into human protein – 20,000 – in one experiment within several weeks.
Mutations in the UBE3B gene were found in three families: in Israel, Italy and Belgium. Recently, symptomatic patients were also found in families in Switzerland, Turkey and Germany. The children in these families suffer from developmental and growth delay, smaller than normal head circumference, droopy eyelids and low levels of cholesterol. In addition, it was found that mice with a delayed expression of the UBE3B gene, reflect the main aspects of the syndrome in humans, such as low weight and a decrease in the level of cholesterol. It is known that cholesterol is a vital component of brain cells and a decrease in the body's production of cholesterol could affect normal brain development.
In another study that involved a Jewish family from Moroccan origin where two sons and an uncle suffered from neurological impairment characterized by mental retardation and smaller than normal head circumference, it was found that the impairment was connected to a mutation of the gene EIF2S3 located on the X chromosome. The researchers found that this genetic mutation affects the ability of the cellular mechanism responsible for the translation of protein to properly identity initial amino acids in protein.
According to Prof. Basel, "Identification of more genes that cause diseases among the different population sectors in Israel is very important to efficiently evaluate rare genetic disease (Orphan Diseases). Discovery of genes connected to mental retardation represent a significant pre-natal diagnostic tool for the prevention of genetic diseases. It also serves a key tool in understanding the biological processes that cause the development of intellectual impairments."
The team in the Genetics Institute at Schneider Children's identified the CC2D1A gene in 2006 that causes genetic mental retardation. Over recent years, the staff in the Institute has identified a gene called SOBP that causes syndromic mental impairment, a gene that causes a fatal degenerative disease in children called NUP62, a gene that causes dandruff of the skin and hair disorders called ST14, and a gene that causes early aging of the skin, hair loss and bone mass loss called R1N2. Also in recent years, Prof. Lina Basel's laboratory has found a link between the PIGN gene and many congenital disorders and a severe convulsive disorder. Institute staff together with physicians in the Institute of Gastroenterology identified the GPD1 gene, responsible for a new liver disease in children that causes an increase in fats in the blood after birth.