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Open Access 01-12-2015 | Research article

Molecular characterization and copy number of SMN1, SMN2 and NAIP in Chinese patients with spinal muscular atrophy and unrelated healthy controls

Authors: Ping Fang, Liang Li, Jian Zeng, Wan-Jun Zhou, Wei-Qing Wu, Ze-Yan Zhong, Ti-Zhen Yan, Jian-Sheng Xie, Jing Huang, Li Lin, Ying Zhao, Xiang-Min Xu

Published in: BMC Musculoskeletal Disorders | Issue 1/2015

Abstract

Background

Spinal muscular atrophy (SMA) is caused by SMN1 dysfunction, and the copy number of SMN2 and NAIP can modify the phenotype of SMA. The aim of this study was to analyze the copy numbers and gene structures of SMA-related genes in Chinese SMA patients and unrelated healthy controls.

Methods

Forty-two Chinese SMA patients and two hundred and twelve unrelated healthy Chinese individuals were enrolled in our study. The copy numbers and gene structures of SMA-related genes were measured by MLPA assay.

Results

We identified a homozygous deletion of SMN1 in exons 7 and 8 in 37 of 42 patients (88.1%); the other 5 SMA patients (11.9%) had a single copy of SMN1 exon 8. The proportions of the 212 unrelated healthy controls with different copy numbers for the normal SMN1 gene were 1 copy in 4 individuals (1.9%), 2 copies in 203 (95.7%) and 3 copies in 5 (2.4%). Three hybrid SMN genes and five genes that lack partial sequences were found in SMA patients and healthy controls. Distributions of copy numbers for normal SMN2 and NAIP were significantly different (P < 0.001) in people with and without SMA.

Conclusion

The copy numbers and gene structures of SMA-related genes were different in Chinese SMA patients and healthy controls.

Lunn MR, Wang CH. Spinal muscular atrophy. Lancet. 2008;371:2120–33.CrossRefPubMed

Sheng-Yuan Z, Xiong F, Chen YJ, Yan TZ, Zeng J, Li L, et al. Molecular characterization of SMN copy number derived from carrier screening and from core families with SMA in a Chinese population. Eur J Hum Genet. 2010;18:978–84.CrossRefPubMedPubMedCentral

Ogino S, Wilson RB. Spinal muscular atrophy: molecular genetics and diagnostics. Expert Rev Mol Diagn. 2004;4:15–29.CrossRefPubMed

Vitte J, Fassier C, Tiziano FD, Dalard C, Soave S, Roblot N, et al. Refined characterization of the expression and stability of the SMN gene products. Am J Pathol. 2007;171:1269–80.CrossRefPubMedPubMedCentral

Elsheikh B, Prior T, Zhang X, Miller R, Kolb SJ, Moore D, et al. An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy. Muscle Nerve. 2009;40:652–6.CrossRefPubMed

Watihayati MS, Zabidi-Hussin AM, Tang TH, Matsuo M, Nishio H, Zilfalil BA. Deletion analyses of SMN1 and NAIP genes in Malaysian spinal muscular atrophy patients. Pediatr Int. 2007;49:4–11.CrossRef

Omrani O, Bonyadi M, Barzgar M. Molecular analysis of the SMN and NAIP genes in Iranian spinal muscular atrophy patients. Pediatr Int. 2009;51:193–6.CrossRefPubMed

Qu YJ, Ge XS, Bai JL, Wang LW, Cao YY, Lu YY, et al. Association of Copy Numbers of Survival Motor Neuron Gene 2 and Neuronal Apoptosis Inhibitory Protein Gene With the Natural History in a Chinese Spinal Muscular Atrophy Cohort. J Child Neurol. 2014; Epub ahead of print.

Gong B, Zhang L, Hou YP, Hu HY, Li HC, Tan MY, et al. Carrier screening for spinal muscular atrophy in 4719 pregnant women in Shanghai region. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2013;30:670–2.PubMed

10.

Wang CC, Jong YJ, Chang JG, Chen YL, Wu SM. Universal fluorescent multiplex PCR and capillary electrophoresis for evaluation of gene conversion between SMN1 and SMN2 in spinal muscular atrophy. Anal Bioanal Chem. 2010;397:2375–83.CrossRefPubMed

11.

Arkblad EL, Darin N, Berg K, Kimber E, Brandberg G, Lindberg C, et al. Multiplex ligation-dependent probe amplification improves diagnostics in spinal muscular atrophy. Neuromuscul Disord. 2006;16:830–8.CrossRefPubMed

12.

Scarciolla O, Stuppia L, De Angelis MV, Murru S, Palka C, Giuliani R, et al. Spinal muscular atrophy genotyping by gene dosage using multiple ligation-dependent probe amplification. Neurogenetics. 2006;7:269–76.CrossRefPubMed

13.

Alías L, Bernal S, Barceló MJ, Also-Rallo E, Martínez-Hernández R, Rodríguez-Alvarez FJ, et al. Accuracy of marker analysis, quantitative real-time polymerase chain reaction, and multiple ligation-dependent probe amplification to determine SMN2 copy number in patients with spinal muscular atrophy. Genet Test Mol Biomarkers. 2011;15:587–94.CrossRefPubMed

14.

Liang YH, Chen XL, Yu ZS, Chen CY, Bi S, Mao LG, et al. Deletion analysis of SMN1 and NAIP genes in Southern Chinese children with spinal muscular atrophy. J Zhejiang Univ Sci B. 2009;10:29–34.CrossRefPubMedPubMedCentral

15.

Jedrzejowska M, Milewski M, Zimowski J, Borkowska J, Kostera-Pruszczyk A, Sielska D, et al. Phenotype modifiers of spinal muscular atrophy: the number of SMN2 gene copies, deletion in the NAIP gene and probably gender influence the course of the disease. Acta Biochim Pol. 2009;56:103–8.PubMed

16.

Chen TH, Tzeng CC, Wang CC, Wu SM, Chang JG, Yang SN, et al. Identification of bidirectional gene conversion between SMN1 and SMN2 by simultaneous analysis of SMN dosage and hybrid genes in a Chinese population. J Neurol Sci. 2011;308:83–7.CrossRefPubMed

17.

He J, Zhang QJ, Lin QF, Chen YF, Lin XZ, Lin MT, et al. Molecular analysis of SMN1, SMN2, NAIP, GTF2H2, and H4F5 genes in 157 Chinese patients with spinal muscular atrophy. Gene. 2013;518:325–9.CrossRefPubMed

18.

Chang JG, Jong YJ, Huang JM, Wang WS, Yang TY, Chang CP, et al. Molecular basis of spinal muscular atrophy in Chinese. Am J Hum Genet. 1995;57:1503–5.PubMedPubMedCentral

19.

Derakhshandeh-Peykar P, Esmaili M, Ousati-Ashtiani Z, Rahmani M, Babrzadeh F, Farshidi S, et al. Molecular analysis of the SMN1 and NAIP genes in Iranian patients with spinal muscular atrophy. Ann Acad Med Singapore. 2007;36:937–41.PubMed

20.

Burghes AH. When is a deletion not a deletion? When it is converted. Am J Hum Genet. 1997;61:9–15.CrossRefPubMedPubMedCentral

21.

Crawford TO, Paushkin SV, Kobayashi DT, Forrest SJ, Joyce CL, Finkel RS, et al. Pilot Study of Biomarkers for Spinal Muscular Atrophy Trial Group. PLoS One. 2012;7(4):e33572.CrossRefPubMedPubMedCentral

22.

Prior TW. Spinal muscular atrophy diagnostics. J Child Neurol. 2007;22:952–6.CrossRefPubMed

23.

Maranda B, Fan L, Soucy JF, Simard L, Mitchell GA. Spinal muscular atrophy: clinical validation of a single-tube multiplex real time PCR assay fordetermination of SMN1 and SMN2 copy numbers. Clin Biochem. 2012;45:88–91.CrossRefPubMed

24.

Khaniani MS, Derakhshan SM, Abasalizadeh S. Prenatal diagnosis of spinal muscular atrophy: clinical experience and molecular genetics of SMN gene analysis in 36 cases. J Prenat Med. 2013;7:32–4.PubMedPubMedCentral

25.

Harada Y, Sutomo R, Sadewa AH, Akutsu T, Takeshima Y, Wada H, et al. Correlation between SMN2 copy number and clinical phenotype of spinal muscular atrophy: three SMN2 copies fail to rescue some patients from the disease severity. J Neurol. 2002;249:1211–9.CrossRefPubMed

26.

Watihayati MS, Fatemeh H, Marini M, Atif AB, Zahiruddin WM, Sasongko TH, et al. Combination of SMN2 copy number and NAIP deletion predicts disease severity in spinal muscular atrophy. Brain Dev. 2009;31:42–5.CrossRefPubMed

Title: Molecular characterization and copy number of SMN1, SMN2 and NAIP in Chinese patients with spinal muscular atrophy and unrelated healthy controls
Authors: Ping Fang
Liang Li
Jian Zeng
Wan-Jun Zhou
Wei-Qing Wu
Ze-Yan Zhong
Ti-Zhen Yan
Jian-Sheng Xie
Jing Huang
Li Lin
Ying Zhao
Xiang-Min Xu
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: BMC Musculoskeletal Disorders / Issue 1/2015
Electronic ISSN: 1471-2474
DOI: https://doi.org/10.1186/s12891-015-0457-x

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Molecular characterization and copy number of SMN1, SMN2 and NAIP in Chinese patients with spinal muscular atrophy and unrelated healthy controls

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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