Ignite Creation Date:
2024-05-06 @ 7:33 AM
Last Modification Date:
2024-10-26 @ 11:49 AM
Study NCT ID:
NCT02550691
Status:
TERMINATED
Last Update Posted:
2019-07-24
First Post:
2015-09-14
Brief Title:
Identification of a Biomarker Associated With Cis-duplication of the SMN1 Gene
Sponsor:
University Hospital Rouen
Organization:
University Hospital Rouen
Study Overview
Official Title:
Identification of a Biomarker Associated With Cis-duplication of the SMN1 Gene Aiming at Improving the Genetic Counseling in Spinal Muscular Atrophy Families
Status:
TERMINATED
Status Verified Date:
2019-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Financial sponsor difficulties
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BADGES
Brief Summary:
Spinal Muscular Atrophy SMA is a neuromuscular disorder characterized by loss of motor neurons in the anterior horn of the spinal cord and leading to muscle atrophy SMA has an autosomal recessive inheritance and affects 1 in 6000 infants with a carrier frequency of 1 in 40 In most cases it is caused by homozygous gene deletion or gene conversion of the SMN1 gene 00 genotype on 5q11-q13 This genomic region has been duplicated and inverted during evolution Thus the SMN1 gene has a very homologous copy called SMN2 Genetic counseling aim at detecting carriers with only one copy of the SMN1 gene 01 genotype SMA carrier testing relies on total copy number quantification of the SMN1 copies by quantitative PCR methods Nevertheless cis-duplication of the SMN1 gene on one allele and deletion on the second allele 20 genotype can lead to a misinterpretation as molecular methods show 2 copies of the SMN1 gene and cannot detect the carrier status
The aim of the study is the characterization of a biomarker specific of the cis-duplication of the SMN1 gene in order to allow the detection of this 20 genotype which constitutes a trap for genetic counseling We will use molecular combing to identify a genomic morse code GMC composed of a combination of probes specific of a structural motif on the cis-duplication chromosome The characterization of this GMC is based on the comparison of two sample groups
The test group with a maximum of 137 individuals carrying 3 copies of the SMN1 gene suggesting a cis-duplication on one allele
The control-1 group with a maximum of 137 individuals carrying 2 copies of the SMN1 gene
A pilot study performed on 24 samples in the two groups is needed to define the exact sample number necessary for statistical analysis of the study When the GMC will be characterized its specificity will be evaluated by testing two sample groups
The test group with 37 individuals carrying 3 copies of the SMN1 gene
The control-2 group with 37 individuals carrying 3 copies of the SMN2 gene Molecular combing needs long DNA fibers and usual methods for DNA extraction are not appropriate This project requires new blood samples for specific DNA extraction
If this project is successful during a second project this GMC will be converted into a simple and cheap PCR-based method We will then evaluate the sensitivity of this method on our sample collection notably on individuals with the 20 genotype defined by familial genotyping
The aim of the study is the characterization of a biomarker specific of the cis-duplication of the SMN1 gene in order to allow the detection of this 20 genotype which constitutes a trap for genetic counseling We will use molecular combing to identify a genomic morse code GMC composed of a combination of probes specific of a structural motif on the cis-duplication chromosome The characterization of this GMC is based on the comparison of two sample groups
The test group with a maximum of 137 individuals carrying 3 copies of the SMN1 gene suggesting a cis-duplication on one allele
The control-1 group with a maximum of 137 individuals carrying 2 copies of the SMN1 gene
A pilot study performed on 24 samples in the two groups is needed to define the exact sample number necessary for statistical analysis of the study When the GMC will be characterized its specificity will be evaluated by testing two sample groups
The test group with 37 individuals carrying 3 copies of the SMN1 gene
The control-2 group with 37 individuals carrying 3 copies of the SMN2 gene Molecular combing needs long DNA fibers and usual methods for DNA extraction are not appropriate This project requires new blood samples for specific DNA extraction
If this project is successful during a second project this GMC will be converted into a simple and cheap PCR-based method We will then evaluate the sensitivity of this method on our sample collection notably on individuals with the 20 genotype defined by familial genotyping
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None