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Trial record 11 of 11 for:    Cavernous Malformation

Genetic Disease Gene Identification

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: NCT00916903
Recruitment Status : Unknown
Verified June 2009 by State University of New York - Upstate Medical University.
Recruitment status was:  Enrolling by invitation
First Posted : June 10, 2009
Last Update Posted : June 10, 2009
Information provided by:
State University of New York - Upstate Medical University

Tracking Information
First Submitted Date June 8, 2009
First Posted Date June 10, 2009
Last Update Posted Date June 10, 2009
Study Start Date October 2005
Estimated Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 9, 2009)
Identification of gene/mutation responsible for disorder.
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title Genetic Disease Gene Identification
Official Title Genetic Disease Gene Identification
Brief Summary

This is a a study to identify inherited disease genes. The study will use molecular techniques to map genetic diseases using techniques such as Affymetrix SNP chips. The powerful combination of the information generated by the Human Genome Project and technical advances such as microarrays enables attempts to identify genes responsible for inherited disorders more possible than ever before. Starting with even modest pedigrees of only a few individuals, or even single individuals, it is possible to identify the gene(s) involved. It is proposed to collect up to 20 ml of peripheral blood and/or buccal cell samples from subjects and relevant family members. Currently the following disorders are approved for investigation.

The current list of disorders:

Aarskog-Scott syndrome, Café-au-Lait spots, Cerebral cavernous malformation, delXp, del2q, del10p, del11q, del12p, del13q, del14q, del16q, del17q, del18q, del Xp21, Choreoathetosis, Congenital Vertical Talus (CVT), Clubfoot, Tarsal coalition and other congenital limb deformities, Cystic Fibrosis (CF)-like disease, Desbuquois syndrome, Droopy Eyelid syndrome (Ptosis), Fanconi-Bickel syndrome (FBS), FENIB (familial encephalopathy with neuroserpin inclusion bodies), FG syndrome, Idiopathic generalised epilepsy (IGE), Renpenning syndrome, transient neonatal diabetes with 6q UPD, translocation (13;14), translocation (3;8), translocation (2;18), Uncharacterized familial dementia and X-linked mental retardation (XLMR).

Detailed Description

It is proposed to identify and recruit individuals and/or families with specified the disorders listed above. 10-20 ml (2-4 teaspoons) of peripheral blood will be collect¬ed from all adult subjects. Smaller volumes of blood would be collected from children based on their age/size. In some cases, as an adequate alternative to collecting peripheral blood, buccal cells will be collected using cheek swabs (Epicentre Biotechnologies). All relevant living members of each pedigree will be asked to partici¬pate, free of charge, on a research basis only. Genomic DNA will be extracted by standard methods and used as template for Polymerase Chain Reac¬tion (PCR) amplification reactions. Individuals will be genotyped at markers and candidate gene sequenced.

Essentially two approaches will be used:

  1. Circumstances that may provide knowledge of candidate genes include reviews of the literature, biology of the disease, understanding of biological pathways, chromosomal rearrangements, mutants in model organisms etc. When candidate genes exist, it is proposed to use linked microsatellite and/or single nucleotide polymorphism (SNP) PCR primer pairs on the DNA from families to determine if there is co-segregation of the disease and markers and thus linkage between the disease gene and previously mapped markers.

    If the disease appears to be linked to the candidate gene, PCR primers flanking all coding exons will be used to amplify the exons and intron/exon boundaries followed by sequencing to detect disease-causing mutations. A web site that enables the design of primers to amplify candidate gene exons is available ( ). If a very strong candidate gene exists, candidate gene sequencing will be performed on affected individual samples without first performing a linkage study.

  2. When no obvious candidate genes exist, and a family of sufficient size has been collected, it is proposed to use Affymetrix SNP microarrays to perform a human genome-wide search for linkage. We have used this approach successfully before (Shrimpton et al 2004), utilizing the whole genome linkage analysis with the Human Mapping 10K Array (Affymetrix Inc., Santa Clara, CA). The 10K Array permits the simultaneous genotyping of more than 11,200 mapped SNPs spaced throughout the human genome at 210 KB intervals. Affymetrix 100K and 500K arrays are also available. SNP genotype information will be analyzed using Varia (Silicon Genetics) and/or Merlin software. The data will be used to define a critical region. If statistically significant segregation is detected, candidate genes within the critical region will be evaluated and ranked in order of their likelihood of being the disease gene. Candidate genes will then be sequenced as detailed above.


  1. Identify candidate disease genes from linkage studies, strong circumstantial evidence or clues from the phenotype.
  2. Sequence candidate genes to detect disease-causing mutations.
  3. Evaluation of detected variation.
Study Type Observational
Study Design Observational Model: Family-Based
Time Perspective: Retrospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
DNA will be isolated from peripheral blood or cheek scraoes.
Sampling Method Non-Probability Sample
Study Population Patients and their families identified by physicians.
  • Congenital Vertical Talus
  • Familial Encephalopathy With Neuroserpin Inclusion Bodies
  • Idiopathic Generalised Epilepsy
  • Familial Dementia
  • X-Linked Mental Retardation
Intervention Not Provided
Study Groups/Cohorts
  • 1
    Patients with genetic condition being studied.
  • 2
    Matched controls
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: June 9, 2009)
Original Estimated Enrollment Same as current
Estimated Study Completion Date October 2010
Estimated Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Patients and their families identified by physicians.

Exclusion Criteria:

  • Patients with unrelated disorders.
Sexes Eligible for Study: All
Ages 6 Months and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
Administrative Information
NCT Number NCT00916903
Other Study ID Numbers IRBPHS#4280F
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Antony E Shrimpton PhD, Assoc Prof, SUNY Upstate Medical University
Study Sponsor State University of New York - Upstate Medical University
Collaborators Not Provided
Principal Investigator: Antony E Shrimpton, PhD State University of New York - Upstate Medical University
PRS Account State University of New York - Upstate Medical University
Verification Date June 2009