SMN Copy Number Distribution in Mali, West Africa

NCT ID: NCT01059240

Last Updated: 2019-12-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 701 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-01-21
• Study Completion Date: 2017-05-18

Brief Summary

Background:

• Spinal muscular atrophy (SMA) is a degenerative and incurable neuromuscular disorder that is caused by mutations in the survival motor neuron gene, SMN1, found on chromosome 5. It is the leading inherited cause of infant mortality. SMA carriers (those who have the genetic mutation but do not have the disease) are often unaware of their status until they are tested.
• Researchers have been studying the prevalence of SMA carriers in the general population, but most of the information collected has come from populations within the United States, Europe, and Asia. Very few studies have been performed in Africa. Furthermore, this information does not provide much information regarding carrier frequency based on ethnic background and ancestry. To address this problem, researchers are interested in studying the prevalence of the SMA genetic mutation in the sub-Saharan nation of Mali.

Objectives:

• To collect blood samples for use in studying genetic data related to spinal muscular atrophy.

Eligibility:

• Healthy volunteers who are at least 18 years of age.
• Volunteers will be of Malian ancestry and nationality.

Study Location:

-<TAB>Bamako, Mali, West Africa

Design:

• The study will first collect blood samples from a small group of volunteers to run initial SMA carrier testing and resolve any technical difficulties before continuing with the study.
• Participants will complete questionnaires about their personal and family medical history, including questions about illnesses, stillborns, and miscarriages, and then will provide blood samples for genetic research and testing.

Detailed Description

Objective

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease that is caused by mutations in the survival motor neuron gene, SMN1. The objective of this study is to determine the SMN copy number distribution in the Malian population and to compare this to published data obtained elsewhere. It is anticipated that this study will help to refine the knowledge of SMA by assessing the distribution of SMN copy number, and the SMA carrier frequency in a sub-Saharan nation, thus expanding the information base available to clinicians and patients considering SMA carrier testing.

Study Population

The study population will include 1400 adult (18 years of age and older) volunteers only.

Design

Blood samples from volunteers will be collected from students at the School of Medicine, Pharmacy, and Dentistry (FMPOS) at the University of Bamako, which consists of an ethnically diverse population representative of the Malian ethnicities. No therapy will be provided to study participants.

Outcome Measures

Outcome measure for phase 1 is DNA extraction yield of sufficient quantity and quality for SMN genotyping by LabCorp in at least 90% of samples. Outcome measures for phase 2 are the frequency of SMA carriers (SMN1 deletion heterozygotes) and the SMN1 and SMN2 copy number distribution in Mali.

Abbreviations and Definition of Terms

• SMA: Spinal Muscular Atrophy
• SMN: Survival Motor Neuron
• SMN1: Survival Motor Neuron Telomeric
• SMN2: Survival Motor Neuron Centromeric

Conditions

Spinal Muscular Atrophy

Study Design

• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

Medical students at the FMPOS of Malian ancestry and nationality who are 18 years of age and above will be considered for this study.

Exclusion Criteria

Subjects may not be eligible to participate if they have a condition that would make a single 6 ml blood draw unsafe. Student assistants are ineligible for the study participation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kenneth H Fischbeck, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Neurological Disorders and Stroke (NINDS)

Locations

University of Bamako, Faculty of Medicine, Pharmacy and Dentistry (FMPOS)

Bamako, , Mali

Countries

Mali

References

Lefebvre S, Burlet P, Liu Q, Bertrandy S, Clermont O, Munnich A, Dreyfuss G, Melki J. Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet. 1997 Jul;16(3):265-9. doi: 10.1038/ng0797-265.

Reference Type: BACKGROUND

PMID: 9207792 (View on PubMed)

Smith M, Calabro V, Chong B, Gardiner N, Cowie S, du Sart D. Population screening and cascade testing for carriers of SMA. Eur J Hum Genet. 2007 Jul;15(7):759-66. doi: 10.1038/sj.ejhg.5201821. Epub 2007 Mar 28.

Reference Type: BACKGROUND

PMID: 17392705 (View on PubMed)

Wirth B, Schmidt T, Hahnen E, Rudnik-Schoneborn S, Krawczak M, Muller-Myhsok B, Schonling J, Zerres K. De novo rearrangements found in 2% of index patients with spinal muscular atrophy: mutational mechanisms, parental origin, mutation rate, and implications for genetic counseling. Am J Hum Genet. 1997 Nov;61(5):1102-11. doi: 10.1086/301608.

Reference Type: BACKGROUND

PMID: 9345102 (View on PubMed)

Other Identifiers

10-N-N033

Identifier Type: -

Identifier Source: secondary_id

999910033

Identifier Type: -

Identifier Source: org_study_id