Spinal Muscular Atrophy Clinical Trial
— BADGESOfficial title:
Identification of a Biomarker Associated With Cis-duplication of the SMN1 Gene Aiming at Improving the Genetic Counseling in Spinal Muscular Atrophy Families
Verified date | July 2019 |
Source | University Hospital, Rouen |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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 (0+0 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 (0+1 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 (2+0 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 2+0 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 2+0 genotype defined by familial
genotyping.
Status | Terminated |
Enrollment | 48 |
Est. completion date | July 4, 2016 |
Est. primary completion date | July 4, 2016 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Adult individual - Individual with either 2 copies of the SMN1 gene (control-1 group), 3 copies of the SMN1 gene (test group), or 3 copies of the SMN2 gene (control-2 group). - Individual with a social insurance - Signed consent form Exclusion Criteria: - Pregnant women, nursing women - Individual without freedom by administrative decision or judicial decision or individual under administrative supervision or legal guardianship |
Country | Name | City | State |
---|---|---|---|
France | Nantes University Hospital | Nantes | |
France | Rouen University Hospital | Rouen |
Lead Sponsor | Collaborator |
---|---|
University Hospital, Rouen | Society GENOMIC VISION |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Identification of a genetic signature indicating the presence of one allele with 2 copies in cis of the SMN1 gene. | Day 1 | ||
Secondary | Specificity of a genetic signature | Specificity of a genetic signature will be done using analysis of individual carrying either 3 copies of the SMN1 gene or 3 copies of the SMN2 gene | Day 1 |
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