Korean J Lab Med.  2010 Feb;30(1):93-96. 10.3343/kjlm.2010.30.1.93.

Determination of SMN1 and SMN2 Copy Numbers in a Korean Population using Multiplex Ligation-dependent Probe Amplification

Affiliations
  • 1Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea. KAL1119@yuhs.ac
  • 2Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea.

Abstract

Determination of the copy number of the survival motor neuron (SMN) gene is important for detecting spinal muscular atrophy (SMA) carriers and compound heterozygous patients. Multiplex ligationdependent probe amplification (MLPA) assay is a simple and efficient technique used for detecting variations in the copy numbers of different genes. Race- and ethnicity-based variation in the SMA carrier frequency and the '2+0' genotype of SMN1 are important factors that should be considered when estimating the risk of being an SMA carrier. Since SMN2 plays a disease-modifying role, accurate determination of SMN2 copy numbers in SMA patients can serve as a useful prognostic tool. Therefore, information on the SMN2 genotype distributions in normal populations will be helpful in selecting appropriate reference samples for MLPA analysis. To determine SMA carrier frequencies and SMN genotype distribution, we determined the copy numbers of SMN1 and SMN2 genes using the MLPA assay in 100 unrelated Korean individuals with no family history of SMA. The frequency of SMA carriers in the Korean population appears to be 1 in 50, which indicates that the prevalence of SMA among Koreans is the same as that among individuals in the Western countries. Two of the 100 normal individuals enrolled in this study showed 3 copies of the SMN1 gene. Therefore, 1.0% of the 198 normal alleles in this population was estimated to be 2-copy alleles ('2+0' genotype). SMN2 copy numbers showed a high degree of individual variation. Our results showed that 64% of the individuals had 2 copies of SMN2, but 36% individuals had between 0, 1, or 3 copies of the gene.

Keyword

Spinal muscular atrophy; Multiplex ligation-dependent probe amplification; Carrier; Copy number; Survival motor neuron gene; Koreans

MeSH Terms

Asian Continental Ancestry Group/*genetics
*Gene Dosage
Heterozygote
Humans
Muscular Atrophy, Spinal/*genetics
Nucleic Acid Amplification Techniques
Republic of Korea
Survival of Motor Neuron 1 Protein/*genetics
Survival of Motor Neuron 2 Protein/*genetics

Figure

  • Fig. 1. Electrophoreogram of SMN1: SMN2=1:3. The carrier is heterozygous for the deletion of the SMN1 gene as shown by reduction in peak heights from 2 probes for exons 7 and 8 (closed arrows). The relative peak height ratios of SMN2 gene increase to approximately 1.5, indicating the presence of 3 copies of SMN2 (open arrows).


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