Finding Genes With NGS Techniques in Whom Mutations Cause Neurological Diseases

In Israel there are various sub-populations with a tendency to consanguinity. Among them are the Arab-Muslim, Druze, Bedouin, Sephardi Jews and to a lesser extent Ashkenazi Jews.

Consanguinity (especially between 2 first cousins) exposes the couple to various genetic diseases at a risk of 25% per each pregnancy. This phenomenon is based on Mendelian autosomal-recessive inheritance. When the couple is from the same family or clan, or even from the same ethnic origin , there is a probability that "dormant" abnormal genes will pass through generations of intermarriage, thus rendering the couple as "carriers" and producing a risk of 25% for the offspring to be affected.

Many of the autosomal-recessive diseases have neurological features such as : developmental delay, intellectual disability, epilepsy and motor and/or sensory impairment. These diseases carry a heavy burden on the family, community and the educational, health and welfare authorities. The disabled children are often handicapped, go to special education programs, are not independent in daily living tasks, are often sick and in need of hospitalization. They will grow up needing special housing facilities. Their life span is usually shorter than normal. These children are dependent on their parents, they subdue the parents to misery, interparental conflicts and susceptibility to divorces. Most of the neurological diseases are untreatable nowadays. Most of the medical effort focuses on their prevention. For example, by finding the gene for a specific neurological condition, we could search for that same gene in the couple's next pregnancy. If the fetus is found to be affected we could offer genetic counseling and a possibility of pregnancy termination and so the family avoids the birth of an affected sibling.

When an individual with a neurogenetic disease is enrolled to the study a careful history is taken to characterize the neurological syndrome, to see if other family members are affected by the same condition, and a pedigree is drawn. We compare the neurological signs and symptoms to information data webs like " PUBMED" or "Online Mendelian Inheritance in Man", and if we don't find a similar description we refer to the family as harboring a new disease with a novel gene.

We work with neurogenetic colleagues abroad like Dr. Andy Singleton in National Institute of Aging, NIH, U.S.A of Dr. Markus Schuelke from Charite Hospital, Berlin, Germany.

We take on ourselves to search for the families, explain to them what are the purposes of the research and their consequences. If we suspect a new gene, we will ask the parents or patients to sign informed consent forms according to our approved Helsinki board. We will take a sample of 10 cc blood in order to extract DNA. The DNA will be extracted in the genetic lab in Israel. A coded DNA will be sent to the researcher abroad. After 12 years the sample will be returned coded to the lab in Israel.

The researchers abroad will use homozygosity mapping techniques as well as NEXT GENERATION SEQUENCING like WHOLE EXOME SEQUENCING and WHOLE GENOME SEQUENCING.

If a new gene is found we will arrange for proper genetic counseling and explain the implications of the genetic data on the individual and his family. We will provide the family with symptomatic or palliative further therapy as needed.