J Korean Med Sci.  2004 Dec;19(6):870-873. 10.3346/jkms.2004.19.6.870.

Quantitative Analysis of SMN1 Gene and Estimation of SMN1 Deletion Carrier Frequency in Korean Population based on Real-Time PCR

  • 1Division of Genetic Disease, Department of Biomedical Sciences, National Institute of Health, Seoul, Korea.
  • 2Graduate School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
  • 3Department of Biochemistry, Ewha Womans University, Seoul, Korea. jungsc@ewha.ac.kr


Spinal muscular atrophy (SMA) is an autosomal recessive disorder, caused by homozygous absence of the survival motor neuron gene (SMN1) in approximately 94% of patients. Since most carriers have only one SMN1 gene copy, several SMN1 quantitative analyses have been used for the SMA carrier detection. We developed a reliable quantitative real-time PCR with SYBR Green I dye and studied 13 patients with SMA and their 24 parents, as well as 326 healthy normal individuals. The copy number of the SMN1 gene was determined by the comparative threshold cycle (Ct) method and albumin was used as a reference gene. The homozygous SMN1 deletion ratio of patients was 0.00 and the hemizygous SMN1 deletion ratio of parents ranged from 0.39 to 0.59. The delta delta Ct ratios of 7 persons among 326 normal individuals were within the carrier range, 0.41-0.57. According to these data, we estimated the carrier and disease prevalence of SMA at 1/47 and 1/8,496 in Korean population, respectively. These data indicated that there would be no much difference in disease prevalence of SMA compared with western countries. Since the prevalence of SMA is higher than other autosomal recessive disorders, the carrier detection method using real-time PCR could be a useful tool for genetic counseling.


Muscular Atrophy, Spinal; SMN Protein; Gene Deletion; Heterozygote; Polymerase Chain Reac-tion; PCR, Real-time

MeSH Terms

Aged, 80 and over
DNA Mutational Analysis/*methods
Genetic Predisposition to Disease/epidemiology
Genetic Screening/*methods
Heterozygote Detection/methods
Middle Aged
Muscular Atrophy, Spinal/*epidemiology/genetics/*metabolism
Nerve Tissue Proteins/*genetics
Polymorphism, Genetic
*Quantitative Trait, Heritable
Reverse Transcriptase Polymerase Chain Reaction/*methods
Risk Assessment/*methods
Risk Factors


  • Fig. 1 Real-time amplification plots of triplicate SMN1 and albumin of: (A) healthy normal control (ΔΔCt ratio 1.04, SD SMN1 0.09, SD albumin 0.01); (B) carrier with one SMN1 copy (ΔΔCt ratio 0.5, SD SMN1 0.01, SD albumin 0.14); (C) patients with SMA of homozygous absence of SMN1 (ΔΔCt ratio 0.00, SD albumin 0.14, no amplification of SMN1).

  • Fig. 2 Identification of specificity of SMN1 primers in three SMA families and a normal individual by multiplex PCR with COL1A1. P, patient; F, father; M, Mother.


1. Pearn J. Classification of spinal muscular atrophies. Lancet. 1980. 1:919–922.
2. Ogino S, Wilson RB. Gnetic testing and risk assessment for spinal muscular atrophy (SMA). Hum Genet. 2002. 111:477–500.
3. Cusin V, Clermont O, Gérard B, Chantereau D, Elion J. Prevalence of SMN1 deletion and duplication in carrier and normal populations: implication for genetic counseling. J Med Genet. 2003. 40:e39.
4. Munsat TL, Davies KE. Meeting report: International SMA Consortium meeting. Neuromuscul Disord. 1992. 2:423–428.
5. Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, Le Paslier D, Frezal J, Cohen D, Weissenbach J, Munnich A, Melki J. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995. 80:155–165.
6. Bürglen L, Lefebvre S, Clermont O, Burlet P, Viollet L, Cruaud C, Munnich A, Melki J. Structure and organization of the human survival motor neurone (SMN) gene. Genomics. 1996. 32:479–482.
7. Lorson CL, Hahnen E, Androphy EJ, Wirth B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci USA. 1999. 96:6307–6311.
8. Monani UR, Lorson CL, Parsons DW, Prior TW, Androphy EJ, Burghes AH, McPherson JD. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet. 1999. 8:1177–1183.
9. Wirth B. An Update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Hum Mutat. 2000. 15:228–237.
10. Shin S, Park SS, Hwang YS, Lee KW, Chung SG, Lee YJ, Park MH. Deletion of SMN and NAIP genes in Korean patients with spinal muscular atrophy. J Korean Med Sci. 2000. 15:93–98.
11. McAndrew PE, Parsons DW, Simard LR, Rochette C, Ray PN, Mendell JR, Prior TW, Burghes AH. Identification of proximal spinal muscular atrophy carriers and patients by analyses of SMNT and SMNC copy number. Am J Hum Genet. 1997. 60:1411–1422.
12. Gérard B, Ginet N, Matthijs G, Evrard P, Baumann C, Da Silva F, Gerard-Blanluet M, Mayer M, Grandchamp B, Elion J. Genotype determination at the survival motor neuron locus in a normal population and SMA carriers using competitive PCR and primer extension. Hum Mutat. 2000. 16:253–263.
13. Scheffer H, Cobben JM, Mensink RG, Stulp RP, van der Steege G, Buys CH. SMA carrier testing-validation of hemizygous SMN exon 7 deletion test for the identification of proximal spinal muscular atrophy carriers and patients with a single allele deletion. Eur J Hum Genet. 2000. 8:79–86.
14. Martin Y, Valero A, del Castillo E, Pascual SI, Hernandez-Chico C. Genetic study of SMA patients without homozygous SMN1 deletions: identification of compound heterozygotes and characterisation of novel intragenic SMN1 deletions. Hum Genet. 2002. 110:257–263.
15. Feldkötter M, Schwarzer V, Wirth R, Wienker TF, Wirth B. Quantitative analyses of SMN1 and SMN2 based on real-time LightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet. 2002. 70:358–368.
16. Anhuf D, Eggermann T, Rudnik-Schöneborn S, Zerres K. Determination of SMN1 and SMN2 copy number using TaqMan™, Technology. Hum Mutat. 2003. 22:74–78.
17. Moon J, Yoon S, Kim E, Shin C, Jo SA, Jo I. Lack of evidence for contribution of Glu298Asp (G894T) polymorphism of endothelial nitric oxide synthase gene to plasma nitric oxide levels. Thromb Res. 2002. 107:129–134.
18. Aarskog NK, Vedeler CA. Real-time quantitative polymerase chain reaction. A new method that detects both the peripheral myelin protein22 duplication in Charcot-Marie-Tooth type 1A disease and the peripheral myelin protein 22 deletion in hereditary neuropathy with liability to pressure palsies. Hum Genet. 2000. 107:494–498.
19. Wirth B, Herz M, Wetter A, Moskau S, Hahnen E, Rudnik-Schöneborn S, Wienker T, Zerres K. Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling. Am J Hum Genet. 1999. 64:1340–1356.
Full Text Links
  • JKMS
export Copy
  • Twitter
  • Facebook
Similar articles
Copyright © 2023 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr