Skip to main content
SpringerLink
Log in

Deletion analysis of SMN1 and NAIP genes in southern Chinese children with spinal muscular atrophy

  • Published:
Journal of Zhejiang University SCIENCE B Aims and scope Submit manuscript

Abstract

Spinal muscular atrophy (SMA) is a disorder characterized by degeneration of lower motor neurons and occasionally bulbar motor neurons leading to progressive limb and trunk paralysis as well as muscular atrophy. Three types of SMA are recognized depending on the age of onset, the maximum muscular activity achieved, and survivorship: SMA1, SMA2, and SMA3. The survival of motor neuron (SMN) gene has been identified as an SMA determining gene, whereas the neuronal apoptosis inhibitory protein (NAIP) gene is considered to be a modifying factor of the severity of SMA. The main objective of this study was to analyze the deletion of SMN1 and NAIP genes in southern Chinese children with SMA. Here, polymerase chain reaction (PCR) combined with restriction fragment length polymorphism (RFLP) was performed to detect the deletion of both exon 7 and exon 8 of SMN1 and exon 5 of NAIP in 62 southern Chinese children with strongly suspected clinical symptoms of SMA. All the 32 SMA1 patients and 76% (13/17) of SMA2 patients showed homozygous deletions for exon 7 and exon 8, and all the 13 SMA3 patients showed single deletion of SMN1 exon 7 along with 24% (4/17) of SMA2 patients. Eleven out of 32 (34%) SMA1 patients showed NAIP deletion, and none of SMA2 and SMA3 patients was found to have NAIP deletion. The findings of homozygous deletions of exon 7 and/or exon 8 of SMN1 gene confirmed the diagnosis of SMA, and suggested that the deletion of SMN1 exon 7 is a major cause of SMA in southern Chinese children, and that the NAIP gene may be a modifying factor for disease severity of SMA1. The molecular diagnosis system based on PCR-RFLP analysis can conveniently be applied in the clinical testing, genetic counseling, prenatal diagnosis and preimplantation genetic diagnosis of SMA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Andreassi, C., Angelozzi, C., Tiziano, F.D., Vitali, T., de Vincenzi, E., Boninsegna, A., Villanova, M., Bertini, E., Pini, A., Neri, G., et al., 2004. Phenylbutyrate increases SMN expression in vitro: relevance for treatment of spinal muscular atrophy. Eur. J. Hum. Genet., 12(1):59–65. [doi:10.1038/sj.ejhg.5201102]

    Article  PubMed  CAS  Google Scholar 

  • Azzouz, M., Le, T., Ralph, G.S., Walmsley, L., Monani, U.R., Lee, D.C., Wilkes, F., Mitrophanous, K.A., Kingsman, S.M., Burghes, A.H., et al., 2004. Lentivector-mediated SMN replacement in a mouse model of spinal muscular atrophy. J. Clin. Invest., 114(12):1726–1731. [doi:10.172/JCI200422922]

    PubMed  CAS  Google Scholar 

  • Battaglia, G., Princivalle, A., Forti, F., Lizier, C., Zeviani, M., 1997. Expression of the SMN gene, the spinal muscular atrophy determining gene, in the mammalian central nervous system. Hum. Mol. Genet., 6(11):1961–1971. [doi:10.1093/hmg/6.11.1961]

    Article  PubMed  CAS  Google Scholar 

  • Burnett, B.G., Sumner, C.J., 2008. Targeting splicing in spinal muscular atrophy. Ann. Neurol., 63(1):3–6. [doi:10.1002/ana.21305]

    Article  PubMed  CAS  Google Scholar 

  • Campbell, L., Potter, A., Ignatius, J., Dubowitz, V., Davies, K., 1997. Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype. Am. J. Hum. Genet., 61(1):40–50. [doi:10.1086/513886]

    Article  PubMed  CAS  Google Scholar 

  • Chan, V., Yip, B., Yam, I., Au, P., Lin, C.K., Wong, V., Chan, T.K., 2004. Carrier incidence for spinal muscular atrophy in southern Chinese. J. Neurol., 251(9):1089–1093. [doi:10.1007/s00415-004-0487-z]

    Article  PubMed  CAS  Google Scholar 

  • Chang, J.G., Jong, Y.J., Huang, J.M., Wang, W.S., Yang, T.Y., Chang, C.P., Chen, Y.J., Lin, S.P., 1995. Molecular basis of spinal muscular atrophy in Chinese. Am. J. Hum. Genet., 57(6):1503–1505.

    PubMed  CAS  Google Scholar 

  • Chang, J.G., Jong, Y.J., Lin, S.P., Soong, B.W., Tsai, C.H., Yang, T.Y., Chang, C.P., Wang, W.S., 1997. Molecular analysis of survival motor neuron (SMN) and neuronal apoptosis inhibitory protein (NAIP) genes of spinal muscular atrophy patients and their parents. Hum. Genet., 100(5–6):577–581. [doi:10.1007/s004390050555]

    Article  PubMed  CAS  Google Scholar 

  • Chen, K.L., Wang, Y.L., Rennert, H., Joshi, I., Mills, J.K., Leonard, D.G., Wilson, R.B., 1999. Duplications and de novo deletions of the SMNt gene demonstrated by fluorescence-based carrier testing for spinal muscular atrophy. Am. J. Med. Genet., 85(5):463–469. [doi:10.1002/(SICI)1096-8628(19990827)85:5〈463::AID-AJMG6〉3.0.CO;2-V]

    Article  PubMed  CAS  Google Scholar 

  • Chen, W.J., Wu, Z.Y., Lin, M.T., Su, J.F., Lin, Y., Murong, S.X., Wang, N., 2007. Molecular analysis and prenatal prediction of spinal muscular atrophy in Chinese patients by the combination of restriction fragment length polymorphism analysis, denaturing high-performance liquid chromatography, and linkage analysis. Arch. Neurol., 64(2):225–321. [doi:10.1001/archneur.64.2.225]

    Article  PubMed  Google Scholar 

  • Chung, B., Wong, V., Ip, P., 2003. Prevalence of neuromuscular diseases in Chinese children: a study in southern China. J. Child Neurol., 18(3):217–219. [doi:10.1177/08830738030180030201]

    Article  PubMed  Google Scholar 

  • Darras, B.T., Kang, P.B., 2007. Clinical trials in spinal muscular atrophy. Curr. Opin. Pediatr., 19(6):675–679.

    Article  PubMed  Google Scholar 

  • Dastur, R.S., Gaitonde, P.S., Khadilkar, S.V., Udani, V.P., Nadkarni, J.J., 2006. Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Indian patients. Neurol. India, 54(3):255–259.

    PubMed  Google Scholar 

  • Frugier, T., Nicole, S., Cifuentes-Diaz, C, Melki, J., 2002. The molecular bases of spinal muscular atrophy. Curr. Opin. Genet. Dev., 12(3):294–298. [doi:10.1016/S0959-437X(02)00301-5]

    Article  PubMed  CAS  Google Scholar 

  • Girardet, A., Fernandez, C., Claustres, M., 2008. Efficient strategies for preimplantation genetic diagnosis of spinal muscular atrophy. Fertil. Steril., 90(2):443.e7–443.e12. [doi:10.1016/j.fertnstert.2007.07.1305]

    Article  Google Scholar 

  • Gotz, R., Karch, C., Digby, M.R., Troppmair, J., Rapp, U.R., Sendtner, M., 2000. The neuronal apoptosis inhibitory protein suppresses neuronal differentiation and apoptosis in PC12 cells. Hum. Mol. Genet., 9(17):2479–2489. [doi:10.1093/hmg/9.17.2479]

    Article  PubMed  CAS  Google Scholar 

  • He, X.H., Zhang, X.N., Mao, W., Chen, H.P., Xu, L.R., Chen, H., He, X.L., Le, Y.P., 2004. A novel mutation of keratin 9 in a large Chinese family with epidermolysis palmoplantar keratoderma. Br. J. Dermatol., 150(4):647–651. [doi:10.1111/j.0007-0963.2004.05865.x]

    Article  PubMed  CAS  Google Scholar 

  • Hsieh-Li, H.M., Chang, J.G., Jong, Y.J., Wu, M.H., Wang, N.M., Tsai, C.H., Li, H., 2000. A mouse model for spinal muscular atrophy. Nat. Genet., 24(1):66–70. [doi:10.038/71709]

    Article  PubMed  CAS  Google Scholar 

  • Huang, C.H., Chang, Y.Y., Chen, C.H., Kuo, Y.S., Hwu, W.L., Gerdes, T., Ko, T.M., 2007. Copy number analysis of survival motor neuron genes by multiplex ligationdependent probe amplification. Genet. Med., 9(4):241–248. [doi:10.1097/GIM.0b013e31803d35bc]

    Article  PubMed  Google Scholar 

  • 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(1):155–165. [doi:10.1016/0092-8674(95)90460-3]

    Article  PubMed  CAS  Google Scholar 

  • Ogino, S., Wilson, R.B., 2004. Spinal muscular atrophy: molecular genetics and diagnosis. Exp. Rev. Mol. Diag., 4(1):15–29. [doi:10.1586/14737159.4.1.15]

    Article  CAS  Google Scholar 

  • Roy, N., Mahadevan, M.S., McLean, M., Shutler, G., Yaraghi, Z., Farahani, R., Baird, S., Besner-Johnston, A., Lefebvre, C., Kang, X., et al., 1995. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell, 80(1):167–178. [doi:10.1016/0092-8674(95)90461-1]

    Article  PubMed  CAS  Google Scholar 

  • Schmutz, J., Martin, J., Terry, A., Couronne, O., Grimwood, J., Lowry, S., Gordon, L.A., Scott, D., Xie, G., Huang, W., et al., 2004. The DNA sequence and comparative analysis of human chromosome 5. Nature, 431(7006):268–274. [doi:10.1038/nature02919]

    Article  PubMed  CAS  Google Scholar 

  • Su, Y.N., Hung, C.C., Li, H., Lee, C.N., Cheng, W.F., Tsao, P.N., Chang, M.C., Yu, C.L., Hsieh, W.S., Lin, W.L., et al., 2005. Quantitative analysis of SMN1 and SMN2 genes based on DHPLC: a highly efficient and reliable carrierscreening test. Hum. Mutat., 25(5):460–467. [doi:10.1002/humu.20160]

    Article  PubMed  CAS  Google Scholar 

  • Talbot, K., Rodrigues, N.R., Ignatius, J., Muntoni, F., Davies, K.E., 1997. Gene conversion at the SMN locus in autosomal recessive spinal muscular atrophy does not predict a mild phenotype. Neuromuscul. Disord., 7(3):198–201. [doi:10.1016/S0960-8966(97)00450-1]

    Article  PubMed  CAS  Google Scholar 

  • Trülzsch, B., Davies, K., Wood, M., 2004. Survival of motor neuron gene downregulation by RNAi: towards a cell culture model of spinal muscular atrophy. Mol. Brain Res., 120(2):145–150. [doi:10.1016/j.molbrainres.2003.10.015]

    Article  PubMed  CAS  Google Scholar 

  • Tsai, C.H., Jong, Y.J., Hu, C.J., Chen, C.M., Shih, M.C., Chang, C.P., Chang, J.G., 2001. Molecular analysis of SMN, NAIP and P44 genes of SMA patients and their families. J. Neurol. Sci., 190(1–2):35–40. [doi:10.1016/S0022-510X(01)00574-3]

    Article  PubMed  CAS  Google Scholar 

  • van der Steege, G., Grootscholten, P.M., van der Vlies, P., Draaijers, T.G., Osinga, J., Cobben, J.M., Scheffer, H., Buys, C.H., 1995. PCR based DNA test to confirm clinical diagnosis of autosomal recessive spinal muscular atrophy. Lancet, 345(8955):985–986. [doi:10.1016/S0140-6736(95)90732-7]

    Article  PubMed  CAS  Google Scholar 

  • Watihayati, M.S., Zabidi-Hussin, A.M., Tang, T.H., Matsuo, M., Nishio, H., Zilfalil, B.A., 2007. Deletion analyses of SMN1 and NAIP genes in Malaysian spinal muscular atrophy patients. Pediatr. Int., 49(1):11–14. [doi:10.1111/j.1442-200X.2007.02302.x]

    Article  PubMed  CAS  Google Scholar 

  • 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(3):228–237. [doi:10.1002/(SICI)1098-1004(200003)15:3〈228::AID-HUMU3〉3.3.CO;2-0]

    Article  PubMed  CAS  Google Scholar 

  • Wong, V., Chan, V., 2001. Molecular genetic study of a childhood form of spinal muscular atrophy. J. Child Neurol., 16(4):291–294. [doi:10.1177/088307380101600412]

    Article  PubMed  CAS  Google Scholar 

  • Yamashita, M., Nishio, H., Harada, Y., Matsuo, M., Yamamoto, T., 2004. Significant increase in the number of the SMN2 gene copies in an adult-onset Type III spinal muscular atrophy patient with homozygous deletion of the NAIP gene. Eur. Neurol., 52(2):101–106. [doi:10.1159/000080140]

    Article  PubMed  Google Scholar 

  • Yu, Z.S., Zhou, B.L., Shui, Q.X., Shang, S.Q., 2001. Gene diagnosis of spinal muscular atrophy in Children. J. Zhejiang Univ. (Med. Sci.), 30(4):158–160 (in Chinese).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Bioscience, Bengbu Medical College, Bengbu, 233000, China

    Yu-hua Liang

  2. Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou, 310058, China

    Yu-hua Liang, Xiao-ling Chen, Chun-yue Chen, Sheng Bi, Lian-gen Mao & Xian-ning Zhang

  3. National Education Base for Basic Medical Sciences, Zhejiang University, Hangzhou, 310058, China

    Yu-hua Liang, Xiao-ling Chen, Chun-yue Chen, Sheng Bi, Lian-gen Mao & Xian-ning Zhang

  4. Children’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China

    Zhong-sheng Yu & Bo-lin Zhou

Authors
  1. Yu-hua Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-ling Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhong-sheng Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chun-yue Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sheng Bi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lian-gen Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bo-lin Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xian-ning Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xian-ning Zhang.

Additional information

The three authors contributed equally to this work

Project supported by the National Natural Science Foundation of China (No. J0710043), and the Natural Science Foundation of Zhejiang Province (No. 2007C33049), China

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liang, Yh., Chen, Xl., Yu, Zs. et al. Deletion analysis of SMN1 and NAIP genes in southern Chinese children with spinal muscular atrophy. J. Zhejiang Univ. Sci. B 10, 29–34 (2009). https://doi.org/10.1631/jzus.B0820125

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1631/jzus.B0820125

Key words

CLC number

Search

Navigation