Ignite Creation Date:
2024-05-05 @ 11:44 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00111384
Status:
COMPLETED
Last Update Posted:
2024-07-15
First Post:
2005-05-19
Brief Title:
Study of Disease Severity in Adults With Neurofibromatosis Type 1 NF1
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Variation in Gene Expression in Neurofibromatosis Type 1
Status:
COMPLETED
Status Verified Date:
2024-06-24
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study may identify genes that predict the seriousness of neurofibromatosis type 1 NF1 Finding these genes may explain why some people with NF1 have more medical problems than others The study will also examine medical problems in NF1 that are rarely seen and are not well understood
Male and female patients with NF1 who have gone through puberty may be eligible for this study as well as patients of any age who have unique or under-recognized disease features Affected and unaffected family members including parents siblings and more distant relatives may also be enrolled Candidates are screened with a discussion of medical history or review of medical records or both Participants undergo the following procedures
Patients with NF1
Physical examination and family history
Photographs of the iris of each eye
Photographs of the back abdomen and thigh to count skin tumors
Photographs of the face and body with underwear on to help track growth and appearance
Magnetic resonance imaging MRI of the spine This test uses a magnetic field and radio waves to look for tumors and curvature of the spine The patient lies still in the scanner a narrow cylindrical device wearing earplugs to muffle loud knocking sounds that occur during the scan A contrast material called gadolinium is injected into a vein through a catheter to enhance the images
Blood draw for genetic studies
Possibly a skin biopsy with the use of numbing medicine removal of a small sample of skin tissue to grow cells in the laboratory
Patients with NF1 who have unique or under-recognized disease features
Physical examination and family history
Blood draw for genetic studies
Possibly a skin biopsy
Possibly additional tests such as blood work x-rays photographs MRIs ultrasounds or other tests
Unaffected family members
Blood draw for genetic studies
Brief skin and eye examinations
Possibly a skin biopsy for cell culture
Families are asked to give permission for researchers to recontact them for follow-up information additional blood samples or follow-up visit
Male and female patients with NF1 who have gone through puberty may be eligible for this study as well as patients of any age who have unique or under-recognized disease features Affected and unaffected family members including parents siblings and more distant relatives may also be enrolled Candidates are screened with a discussion of medical history or review of medical records or both Participants undergo the following procedures
Patients with NF1
Physical examination and family history
Photographs of the iris of each eye
Photographs of the back abdomen and thigh to count skin tumors
Photographs of the face and body with underwear on to help track growth and appearance
Magnetic resonance imaging MRI of the spine This test uses a magnetic field and radio waves to look for tumors and curvature of the spine The patient lies still in the scanner a narrow cylindrical device wearing earplugs to muffle loud knocking sounds that occur during the scan A contrast material called gadolinium is injected into a vein through a catheter to enhance the images
Blood draw for genetic studies
Possibly a skin biopsy with the use of numbing medicine removal of a small sample of skin tissue to grow cells in the laboratory
Patients with NF1 who have unique or under-recognized disease features
Physical examination and family history
Blood draw for genetic studies
Possibly a skin biopsy
Possibly additional tests such as blood work x-rays photographs MRIs ultrasounds or other tests
Unaffected family members
Blood draw for genetic studies
Brief skin and eye examinations
Possibly a skin biopsy for cell culture
Families are asked to give permission for researchers to recontact them for follow-up information additional blood samples or follow-up visit
Detailed Description:
We hypothesize that normal germline variation in gene expression accounts in part for variation in the clinical severity and phenotype of the monogenic disorder neurofibromatosis type 1 NF1 The phenotype of NF1 is constituted by a variety of quantifiable features we term these features sub-phenotypes Our main focus is on sub-phenotypes with published evidence of variation in expression from an inherited component These include our primary sub-phenotype of spinal neurofibroma burden quantified by MRI of spinal neurofibromas and the secondary sub-phenotypes of dermal neurofibroma burden head circumference number of Lisch nodules scoliosis history of plexiform neurofibromas and height Other sub-phenotypes as collected by a routine history and physical will also be evaluated
According to our hypothesis the severity of a sub-phenotype will correlate with heritable differences in the germline expression of certain genes As an example consider a spectrum of individuals affected with the primary sub-phenotype of spinal neurofibroma burden For most genes there will be no relationship of expression level to the number of spinal neurofibromas However some genes will have a direct or inverse or other correlation of their level of expression and the number of neurofibromas Such genes would be considered as candidate modifier genes The secondary sub-phenotypes will also be analyzed in a similar way To limit false positives candidate genes will then be tested for association using the transmissiondisequilibrium test TDT with the appropriate sub-phenotype
Recruitment will be focused on identifying individuals with a range of severity of the primary sub-phenotype spinal neurofibroma burden We will primarily recruit post-pubertal individuals who meet the 1988 NIH criteria for neurofibromatosis type 1 NIH Consensus Development Conference 1988 We will exclude those with recognized segmental or mosaic NF1 The rate of cutaneous neurofibroma growth and number is known to vary widely these tumors typically appear in adolescence For this reason we will ascertain patients after puberty We expect most individuals to be 18 years or older but will also accept post-pubertal pediatric patients and use a hand film to demonstrate bone age Parents whether affected or not are critical when using family-based tests of association like the TDT and tests of linkage and will also be recruited
Tests of association with the TDT require trios mother father proband Multiple trios can be derived from a single family if there are multiple affected individuals within the family We set a recruitment goal of 100 trios and a ceiling of 1500 individuals 500 affected individuals plus 1000 parents or additional sibs in about 400 families
In the interest of improving care for people living with NF1 this protocol also seeks to characterize at the PI s discretion individuals with unique or under-recognized features of NF1 as well as individuals with NF1-like phenotypes including those patients with a known or suspected RAS pathway disorder
According to our hypothesis the severity of a sub-phenotype will correlate with heritable differences in the germline expression of certain genes As an example consider a spectrum of individuals affected with the primary sub-phenotype of spinal neurofibroma burden For most genes there will be no relationship of expression level to the number of spinal neurofibromas However some genes will have a direct or inverse or other correlation of their level of expression and the number of neurofibromas Such genes would be considered as candidate modifier genes The secondary sub-phenotypes will also be analyzed in a similar way To limit false positives candidate genes will then be tested for association using the transmissiondisequilibrium test TDT with the appropriate sub-phenotype
Recruitment will be focused on identifying individuals with a range of severity of the primary sub-phenotype spinal neurofibroma burden We will primarily recruit post-pubertal individuals who meet the 1988 NIH criteria for neurofibromatosis type 1 NIH Consensus Development Conference 1988 We will exclude those with recognized segmental or mosaic NF1 The rate of cutaneous neurofibroma growth and number is known to vary widely these tumors typically appear in adolescence For this reason we will ascertain patients after puberty We expect most individuals to be 18 years or older but will also accept post-pubertal pediatric patients and use a hand film to demonstrate bone age Parents whether affected or not are critical when using family-based tests of association like the TDT and tests of linkage and will also be recruited
Tests of association with the TDT require trios mother father proband Multiple trios can be derived from a single family if there are multiple affected individuals within the family We set a recruitment goal of 100 trios and a ceiling of 1500 individuals 500 affected individuals plus 1000 parents or additional sibs in about 400 families
In the interest of improving care for people living with NF1 this protocol also seeks to characterize at the PI s discretion individuals with unique or under-recognized features of NF1 as well as individuals with NF1-like phenotypes including those patients with a known or suspected RAS pathway disorder
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 05-C-0152 | None | None | None |