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Finding Genes With NGS Techniques in Whom Mutations Cause Neurological Diseases (NGS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02340871
Recruitment Status : Unknown
Verified December 2014 by Rabin Medical Center.
Recruitment status was:  Not yet recruiting
First Posted : January 19, 2015
Last Update Posted : January 19, 2015
Charite University, Berlin, Germany
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Rabin Medical Center

Brief Summary:

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.

Condition or disease Intervention/treatment
Neurological Diseases Genetic: Genetic testing

Detailed Description:

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.

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Study Type : Observational
Estimated Enrollment : 75 participants
Time Perspective: Prospective
Official Title: Finding Genes With NGS Techniques in Whom Mutations Cause Neurological Diseases
Study Start Date : March 2015
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine

Group/Cohort Intervention/treatment
Genetic Neurological Diseases
The group consists of patients with a neurological disease that are tested for finding the genetic basis of their disease.The neurological signs and symptoms include ataxia, intellectual disability, seizures, movement disorders, migrational disorders, macrocephaly, microcephaly and various other signs and symptoms. The group consists of patients from 1-year-old until 90 years who are having a neurological disease as stated above or who are the parents or siblings of the affected patients. Blood specimens will be taken from them and DNA will be extracted for next generation studies like whole exome sequence or whole genome sequence. This process is called genetic testing. The current proposal will assist in diagnosing children and families with a neurological disease for genetic counseling.
Genetic: Genetic testing
Patients suspected of harboring a genetic neurological disease will be summoned to take a blood test. DNA will be extracted from the blood and sent to the collaborating hospital labs for next generation sequencing.

Primary Outcome Measures :
  1. 75 patients with a neurological disease will be tested by Next Generation Sequence techniques to find a genetic basis for their disease [ Time Frame: 3 years ]
    The outcome (the finding of a new gene will be reported to the patient and his caregivers.

Biospecimen Retention:   Samples With DNA
Samples with DNA

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 90 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patients with a constellation of neurological findings that seem to be a new syndrome or disease are enrolled to the study to decipher the genetic basis of their disease with next generation techniques.

Inclusion Criteria:All patients with neurological conditions, their siblings and parents. -

Exclusion Criteria:None


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02340871

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Contact: Rachel Straussberg, M.D 972-3-9253870
Contact: Yoram Nevo, M.D 972-3-9253613

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Scneider's Children Medical Center
Petah - Tikva, Israel, 4920235
Contact: Rachel Straussberg, M.D    972-3-9253870   
Contact: Yoram Nevo, M.D    972-3-9253613   
Sponsors and Collaborators
Rabin Medical Center
Charite University, Berlin, Germany
National Institute on Aging (NIA)
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Principal Investigator: Rachel Straussberg, M.D Schneider's Children Medical Center
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Responsible Party: Rabin Medical Center Identifier: NCT02340871    
Other Study ID Numbers: 0643-13
1ZIAAG000958-12 ( U.S. NIH Grant/Contract )
First Posted: January 19, 2015    Key Record Dates
Last Update Posted: January 19, 2015
Last Verified: December 2014
Keywords provided by Rabin Medical Center:
genetic testing
Additional relevant MeSH terms:
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Nervous System Diseases