Spinal Muscular AtrophyNCT00155168
Quantitative Analysis of SMN1 and SMN2 Gene Based on DHPLC System
An observational study of Spinal Muscular Atrophy, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
In this project, we will establish the efficient and accurate gene dose determination system by combining the heterodulex analysis and gene dose analysis on DHPLC platform based on various quantitative and multiplex PCR strategies and applying on detecting the carriers- in- risk and patients with spinal muscular… Read more about this study
- Who is it for?
- Ages 0 years and olderHealthy volunteers can take part
- Conditions the study is for
- Spinal Muscular Atrophy
- How many people
- 500 participants
- Where
- 1 siteTaiwan
- Study dates
- Apr 2004to not given
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Clinical diagnosis of Spinal muscular atrophy
Who cannot join
- nil
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Dept of Medical Genetics;National Taiwan University Hospital
Taipei, 100
Yi-Ning su, MD,PhD, 886-2-23123456 ext. 7675, ynsu@ntumc.org
About this study
Official title: Quantitative Analysis of SMN1 and SMN2 Gene Based on DHPLC System: Establishing a Novel Highly Efficient and Reliable SMA Carrier Screening Test
In this project, we will establish the efficient and accurate gene dose determination system by combining the heterodulex analysis and gene dose analysis on DHPLC platform based on various quantitative and multiplex PCR strategies and applying on detecting the carriers- in- risk and patients with spinal muscular atrophy.This method is, therefore, based on the observation that the amount of PCR product generated from each site of amplification is proportional to the amount of starting template. Detection of PCR products is carried out on DHPLC, which provide the sensitivity required for the detection of the single-copy dosage changes.
Read the detailed description
Proximal spinal muscular atrophy is an autosomal recessive disorder with an overall incidence of 1 in 10000 live births and a carrier frequency of 1 in 50. This severe neuromuscular disease is characterized by a degeneration and loss of alpha motor neurons of the spinal cord anterior horn cells, which results in progressive symmetrical weakness, atrophy of the proximal voluntary muscles, and infant death.
Two most identical copies of SMN gene, telomeric SMN (SMN1) and centromeric SMN (SMN2), have been identified. These two SMN genes are highly homologous and differing in only five nucleotide exchanges within their 3' regions. These variations do not alter the encoded amino acids. These nucleotide differences located in exons 7 and 8, allow SMN1 gene to be distinguished from SMN2 gene.
It has been reported that more than 95% of SMA patients were homozygous deletion of SMN1 gene. Therefore, the detection of the absence of SMN1 can be a useful tool for SMA diagnosis. Furthermore, because of the high incidence of SMA, the high carrier frequency of at least 1 in 50, the severity of the disease in the patients, and the lack of effective of treatment, carrier testing for SMN1 deletion is an important question in genetic counseling. However, a highly homologous SMN2 gene also exits and hampers the detection of the loss of SMN1 which makes the detection of SMA carrier test difficult.
Here, we present a new, rapid, simple and high reliable method to detect the SMN1 deletion and to determine the copy number of the SMN1 and SMN2 by denaturing high-performance liquid chromatography (DHPLC). DHPLC is a novel, simple, fast and non gel-base method that is very sensitive and specific for detection DNA variations. Furthermore, we describe a multiplex PCR strategy to determine the SMN1 and SMN2 genes copy number in order to avoid bias due to fluctuations in the copy number of SMN genes. The assay uses the X-linked CYBB gene and KRIT1 gene as standards to determine the relative gene dosage of SMN1 and SMN2 genes. We demonstrate that this assay is able to accurately distinguish 2 gene copies from 4 gene copies and it can identify SMA carriers and normal populations by the accurate determination of SMN copy number.
This project will contribute to apply this novel, fast, and reliable tool for diagnosis of SMA and carrier detection of SMN1 and SMN2 genes by using DHPLC system.
- Conditions
- Spinal Muscular Atrophy
- Keywords
- Spinal muscular atrophy (SMA), SMN1/SMN2 gene, denaturing high-performance liquid chromatography (DHPLC), multiplex PCR, gene dose, carrier test
- Medical subject headings
- Muscular Atrophy, Spinal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study startApr 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 500 participants
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Yi-Ning su, MD,PhD, Study chair, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00155168
- Sponsor's protocol ID
- 9361700452
- Status last verified
- Apr 2004
- First submitted
- 9 Sep 2005
- Last updated
- 12 Sep 2005
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantitative Analysis of SMN1 and SMN2 Gene Based on DHPLC System: Establishing a Novel Highly Efficient and Reliable SMA Carrier Screening Test
- ClinicalTrials.gov ID
- NCT00155168
- Acronym / sponsor ID
- 9361700452
- Conditions
- Spinal Muscular Atrophy
- Keywords
- Spinal muscular atrophy (SMA), SMN1/SMN2 gene, denaturing high-performance liquid chromatography (DHPLC), multiplex PCR, gene dose, carrier test
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 500 participants
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Apr 2004
- First posted
- 12 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this project, we will establish the efficient and accurate gene dose determination system by combining the heterodulex analysis and gene dose analysis on DHPLC platform based on various quantitative and multiplex PCR strategies and applying on detecting the carriers- in- risk and patients with spinal muscular atrophy.This method is, therefore, based on the observation that the amount of PCR product generated from each site of amplification is proportional to the amount of starting template. Detection of PCR products is carried out on DHPLC, which provide the sensitivity required for the detection of the single-copy dosage changes.
Detailed description
Proximal spinal muscular atrophy is an autosomal recessive disorder with an overall incidence of 1 in 10000 live births and a carrier frequency of 1 in 50. This severe neuromuscular disease is characterized by a degeneration and loss of alpha motor neurons of the spinal cord anterior horn cells, which results in progressive symmetrical weakness, atrophy of the proximal voluntary muscles, and infant death.
Two most identical copies of SMN gene, telomeric SMN (SMN1) and centromeric SMN (SMN2), have been identified. These two SMN genes are highly homologous and differing in only five nucleotide exchanges within their 3' regions. These variations do not alter the encoded amino acids. These nucleotide differences located in exons 7 and 8, allow SMN1 gene to be distinguished from SMN2 gene.
It has been reported that more than 95% of SMA patients were homozygous deletion of SMN1 gene. Therefore, the detection of the absence of SMN1 can be a useful tool for SMA diagnosis. Furthermore, because of the high incidence of SMA, the high carrier frequency of at least 1 in 50, the severity of the disease in the patients, and the lack of effective of treatment, carrier testing for SMN1 deletion is an important question in genetic counseling. However, a highly homologous SMN2 gene also exits and hampers the detection of the loss of SMN1 which makes the detection of SMA carrier test difficult.
Here, we present a new, rapid, simple and high reliable method to detect the SMN1 deletion and to determine the copy number of the SMN1 and SMN2 by denaturing high-performance liquid chromatography (DHPLC). DHPLC is a novel, simple, fast and non gel-base method that is very sensitive and specific for detection DNA variations. Furthermore, we describe a multiplex PCR strategy to determine the SMN1 and SMN2 genes copy number in order to avoid bias due to fluctuations in the copy number of SMN genes. The assay uses the X-linked CYBB gene and KRIT1 gene as standards to determine the relative gene dosage of SMN1 and SMN2 genes. We demonstrate that this assay is able to accurately distinguish 2 gene copies from 4 gene copies and it can identify SMA carriers and normal populations by the accurate determination of SMN copy number.
This project will contribute to apply this novel, fast, and reliable tool for diagnosis of SMA and carrier detection of SMN1 and SMN2 genes by using DHPLC system.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
Who may qualify
- Ages
- 0 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Clinical diagnosis of Spinal muscular atrophy
Key exclusion criteria (1 listed)
- nil
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2005.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yi-Ning su, MD,PhD study chair
National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Spinal Muscular Atrophy, run by National Taiwan University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Sep 2005. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yi-Ning su, MD,PhD (886-2-23123456 ext. 7675, ynsu@ntumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2005.