Skip to main content

Carrier incidence for spinal muscular atrophy in southern Chinese

Journal of Neurology volume 251, pages 1089–1093 (2004)Cite this article

Abstract.

A real time quantitative PCR (QPCR) method using TaqMan technology was used to assess the copy number of the two survival motor neuron genes (SMN1 and SMN2) on chromosome 5q13. This allows the accurate determination of carriers for spinal muscular atrophy (SMA), with one copy of SMN1. Analysis of 569 normal southern Chinese individuals revealed a carrier incidence of 1.6%, similar to that found in the western society. Study of 42 obligatory carriers showed a (2 + 0) genotype in two (4.8 %). In 27 SMA patients with homozygous deletion of the SMN1 gene, the number of SMN2 gene correlated with disease phenotype, with 68% of type II and III patients carrying three or more SMN2 genes, whilst the incidence of three or more SMN2 genes in the normal population was 1.57%.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Bassler HA, Flood SJ, Livak KJ, Marmaro J, Knorr R, Batt CA (1995) Use of a fluorogenic probe in a PCR-based assay for the detection of Listeria monocytogenes. Appl Environ Microbiol 61:3724–3728

    CAS  PubMed  Google Scholar 

  2. Burglen L, Lefebvre S, Clermont O, Burlet P, Viollet L, Cruaud C, Munnich A, Melki J (1996) Structure and organization of the human survival motor neurone (SMN) gene. Genomics 32:479–482

    Article  CAS  PubMed  Google Scholar 

  3. Chan V, Yip B, Lam YH, Tse HY, Wong HS, Chan TK (2001) Quantitative polymerase chain reaction for the rapid prenatal diagnosis of homozygous alpha-thalassaemia (Hb Barts hydrops fetalis). Br J Haematol 115:341–346

    Article  CAS  PubMed  Google Scholar 

  4. Chen Q, Baird SD, Mahadevan M, Besner-Johnston A, Farahani R, Xuan J, Kang X, Lefebvre C, Ikeda JE, Korneluk RG, MacKenzie AE (1998) Sequence of a 131-kb region of 5q13.1 containing the spinal muscular atrophy candidate genes SMN and NAIP. Genomics 48:121–127

    Article  CAS  PubMed  Google Scholar 

  5. Feldkotter M, Schwarzer V, Wirth R, Wienker TF, Wirth B (2002) 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 70:358–368

    Article  CAS  PubMed  Google Scholar 

  6. Heid CA, Stevens J, Livak KJ, Williams PM (1996) Real time quantitative PCR. Gen Res 6:986–994

    CAS  Google Scholar 

  7. Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, et al. (1995) Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80:155–165

    Article  CAS  PubMed  Google Scholar 

  8. Lorson CL, Strasswimmer J, Yao LM, Baleja JD, Hahnen E, Wirth B, Le T, Burghes AH, Androphy EJ (1998) SMN oligomerization defect correlates with spinal muscular atrophy severity. Nat Genet 19:63–67

    CAS  PubMed  Google Scholar 

  9. Lorson CL, Hahnen E, Androphy EJ, Wirth B (1999) A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci, USA 96:6307–6311

    Article  CAS  PubMed  Google Scholar 

  10. Mailman MD, Heinz JW, Papp AC, Snyder PJ, Sedra MS, Wirth B, Burghes AHM, Prior TW (2002) Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med 4:20–26

    Article  CAS  PubMed  Google Scholar 

  11. McAndrew PE, Parsons DW, Simard LR, Rochette C, Ray PN, Mendell JR, Prior TW, Burghes AHM (1997) Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number. Am J Hum Genet 60:1411–1422

    CAS  PubMed  Google Scholar 

  12. Monani UR, Lorson CL, Parsons DW, Prior TW, Androphy EJ, Burghes AH, McPherson JD (1999) A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet 8:1177–1183

    Article  CAS  PubMed  Google Scholar 

  13. Munsat TL, Davies KE (1992) International SMA consortium meeting. Neuromusc Disord 2:423–428

    CAS  PubMed  Google Scholar 

  14. Ogino S, Wilson RB (2002) SMN dosage analysis and risk assessment for spinal muscular atrophy. Am J Hum Genet 70:1596–1597

    Article  CAS  PubMed  Google Scholar 

  15. van der Steege G, Grootscholten PM, van der Vlies P, Draaijers TG, Osinga J, Cobben JM, Scheffer H, Buys CHCM (1995) PCR-based DNA test to confirm clinical diagnosis of autosomal recessive spinal muscular atrophy. Lancet 345:985–986

    Article  CAS  Google Scholar 

  16. Wirth B (2000) An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Hum Mutat 15:228–237

    Article  CAS  PubMed  Google Scholar 

  17. Wirth B, Herz M, Wetter A, Moskau S, Hahnen E, Rudnik-Schoneborn S, Wienker T, Zerres K (1999) 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 64:1340–1356

    Article  CAS  PubMed  Google Scholar 

  18. Wong VCN, Chan VNY (2001) Molecular genetic study of a childhood form of spinal muscular atrophy. J Child Neurol 16:291–294

    CAS  PubMed  Google Scholar 

  19. Zerres K, Davies KE (1999) Workshop report. 59th ENMC International Workshop: spinal muscular atrophies: clinical and genetic correlations. Neuromusc Disord 9:272–278

    Article  CAS  PubMed  Google Scholar 

  20. Zerres K, Rudnik-Schoneborn S (1995) Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol 52:518–523

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

  1. University Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong

    Vivian Chan, Ben Yip, Irene Yam, Patrick Au & Tai-Kwong Chan

  2. Department of Paediatrics & Adolescent Medicine, Queen Mary Hospital, Hong Kong

    Virginia Wong

  3. Hong Kong Red Cross Blood Transfusion Service, Hong Kong

    Che-Kit Lin

Authors
  1. Vivian Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ben Yip
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Irene Yam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patrick Au
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Che-Kit Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Virginia Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tai-Kwong Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vivian Chan.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chan, V., Yip, B., Yam, I. et al. Carrier incidence for spinal muscular atrophy in southern Chinese. J Neurol 251, 1089–1093 (2004). https://doi.org/10.1007/s00415-004-0487-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-004-0487-z

Key words

  • QPCR
  • SMN1
  • SMN2
  • SMA carriers
  • phenotype