Finding Genes With NGS Techniques in Whom Mutations Cause Neurological Diseases
Finding Genes With NGS Techniques in Whom Mutations Cause Neurological Diseases
In Israel, because of special qualification in neurogenetics, during a 30 year career ,we
 have found, characterized and treated at least 13 novel neurological diseases. The genetic
 basis was elucidated with geneticist colleagues both in Israel and worldwide. The diseases we
 have found encompass all the fields of pediatric neurology including intellectual disability,
 epilepsy, muscle-nerve disorders, malformations of the brain, microcephaly, macrocephaly,
 cerebellar ataxia, chorea. dystonia, cerebral palsy and many other symptoms and signs.

 We are especially interested in consanguineous families, in whom the parents are first or
 second degree cousins. These families often bear autosomal - recessive diseases. If the
 family is informative - with 2 or more affected children - then with current genetic
 techniques there is a good chance of finding the causative gene to this specific disease.
 This is not only a theoretical - academic accomplishment. In practice, after discovering the
 gene, the family is given genetic counseling and in their further pregnancies the geneticists
 will examine either by preimplantation genetic diagnosis (PGD) or amniocentesis if the embryo
 is affected or not. In the early stages of the pregnancy if the embryo is indeed affected by
 the disease caused by the gene we have found and the religious official consents, genetic
 counseling can offer termination of pregnancy to the couple.

 Needless to say, we know the immense burden of an affected child on the family, community and
 society. The parents are guilt-ridden, the affected child draws extensive resources from
 educational, health and rehabilitation authorities. We can contribute to the well-being of
 the family and the clan (because many times the relatives are affected).

 We can perform sophisticated genetic studies such as Whole Genome Sequencing and Whole Exome
 Sequencing.After an informative family is recruited to the study, we will explain the aims of
 the research. The parents and eligible patients will sign informed consent forms, according
 to the local Helsinki Board. Blood samples will be taken in Israel, DNA extracted in the
 Israeli lab and then shipped coded to the researchers in USA or Germany. If the researchers
 will find a new gene the family will be notified and given appropriate genetic counseling. We
 will continue to follow and treat the family onwards.
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.
Inclusion Criteria:All patients with neurological conditions, their siblings and parents. -

 Exclusion Criteria:None

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