Tags

Type your tag names separated by a space and hit enter

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(9):1211-9JN

Abstract

Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder that is characterized by degeneration of the anterior horn cells of the spinal cord, which leads to the axial and limb weakness associated with muscle atrophy. SMA is classified into three groups based on the clinical severity: type I (severe), type II (intermediate) and type III (mild). All three clinical subtypes of SMA are caused by mutations of the SMN1 gene. More than 95 % of SMA patients show homozygous deletion of SMN1. It is thought that SMN2, which is a highly homologous gene of SMN1, compensates for the SMN1 deletion to some degree. To clarify the relationship between SMN2 and the disease severity of SMA, we performed fluorescence-based quantitative polymerase chain reaction assay of the copy number of SMN2 in 27 patients (11 type I and 16 type II-III) homozygous for SMN1 deletion. The SMN2 copy number in type II-III patients was 3.1 +/- 0.3 (mean +/- SD), which is significantly higher than that observed in type I patients, 2.2 +/- 0.6 (P < 0.01). However, three of the 11 type I patients carried 3 SMN2 copies. A type I patient with 3 SMN2 copies was studied further. RT-PCR analysis of the patient showed a trace of full-length SMN2 mRNA species, but a large amount of the truncated SMN2 mRNA species lacking exon 7. In conclusion, SMN2 alleles are not functionally equivalent among SMA patients, although in general the SMN2 copy number is correlated with the severity of SMA. Genetic background influencing splicing mechanisms of the SMN2 gene may be more critical in some SMA patients.

Authors+Show Affiliations

Division of Public Health, Department of Environmental Health and Safety, Faculty of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12242541

Citation

Harada, Yosuke, 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." Journal of Neurology, vol. 249, no. 9, 2002, pp. 1211-9.
Harada Y, Sutomo R, Sadewa AH, 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(9):1211-9.
Harada, Y., Sutomo, R., Sadewa, A. H., Akutsu, T., Takeshima, Y., Wada, H., ... Nishio, H. (2002). Correlation between SMN2 copy number and clinical phenotype of spinal muscular atrophy: three SMN2 copies fail to rescue some patients from the disease severity. Journal of Neurology, 249(9), pp. 1211-9.
Harada Y, 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(9):1211-9. PubMed PMID: 12242541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Correlation between SMN2 copy number and clinical phenotype of spinal muscular atrophy: three SMN2 copies fail to rescue some patients from the disease severity. AU - Harada,Yosuke, AU - Sutomo,Retno, AU - Sadewa,Ahmad Hamim, AU - Akutsu,Tomoko, AU - Takeshima,Yasuhiro, AU - Wada,Hiroko, AU - Matsuo,Masafumi, AU - Nishio,Hisahide, PY - 2002/9/21/pubmed PY - 2002/12/28/medline PY - 2002/9/21/entrez SP - 1211 EP - 9 JF - Journal of neurology JO - J. Neurol. VL - 249 IS - 9 N2 - Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder that is characterized by degeneration of the anterior horn cells of the spinal cord, which leads to the axial and limb weakness associated with muscle atrophy. SMA is classified into three groups based on the clinical severity: type I (severe), type II (intermediate) and type III (mild). All three clinical subtypes of SMA are caused by mutations of the SMN1 gene. More than 95 % of SMA patients show homozygous deletion of SMN1. It is thought that SMN2, which is a highly homologous gene of SMN1, compensates for the SMN1 deletion to some degree. To clarify the relationship between SMN2 and the disease severity of SMA, we performed fluorescence-based quantitative polymerase chain reaction assay of the copy number of SMN2 in 27 patients (11 type I and 16 type II-III) homozygous for SMN1 deletion. The SMN2 copy number in type II-III patients was 3.1 +/- 0.3 (mean +/- SD), which is significantly higher than that observed in type I patients, 2.2 +/- 0.6 (P < 0.01). However, three of the 11 type I patients carried 3 SMN2 copies. A type I patient with 3 SMN2 copies was studied further. RT-PCR analysis of the patient showed a trace of full-length SMN2 mRNA species, but a large amount of the truncated SMN2 mRNA species lacking exon 7. In conclusion, SMN2 alleles are not functionally equivalent among SMA patients, although in general the SMN2 copy number is correlated with the severity of SMA. Genetic background influencing splicing mechanisms of the SMN2 gene may be more critical in some SMA patients. SN - 0340-5354 UR - https://www.unboundmedicine.com/medline/citation/12242541/Correlation_between_SMN2_copy_number_and_clinical_phenotype_of_spinal_muscular_atrophy:_three_SMN2_copies_fail_to_rescue_some_patients_from_the_disease_severity_ L2 - https://dx.doi.org/10.1007/s00415-002-0811-4 DB - PRIME DP - Unbound Medicine ER -