Better survival in female SOD1-mutant patients with ALS: a study of SOD1-related natural history
Abstract Background SOD1 mutations are the most common cause of amyotrophic lateral sclerosis (ALS) in non-Caucasian patients. Detailed natural history profiles of SOD1-mutant patients will be beneficial for the strategy and interpretation of future SOD1-targeted clinical practice. Methods Mutationa...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Translational Neurodegeneration |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40035-018-0142-8 |
| _version_ | 1818902448801054720 |
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| author | Lu Tang Yan Ma Xiao-lu Liu Lu Chen Dong-sheng Fan |
| author_facet | Lu Tang Yan Ma Xiao-lu Liu Lu Chen Dong-sheng Fan |
| author_sort | Lu Tang |
| collection | DOAJ |
| description | Abstract Background SOD1 mutations are the most common cause of amyotrophic lateral sclerosis (ALS) in non-Caucasian patients. Detailed natural history profiles of SOD1-mutant patients will be beneficial for the strategy and interpretation of future SOD1-targeted clinical practice. Methods Mutational distribution, age at onset (AAO), site of onset, diagnostic delay, disease progression (rate of ALSFRS-R decrease, ΔFS) and survival were analysed. Further comparisons between heredity of disease, gender, and mutations were performed. Results Sixty-six cases with 43 SOD1 mutations were included and analysed, with p.His47Arg as the leading mutation and seven novel variants identified. The mean (SD) AAO was 43.92 years (9.24) for all subjects, with a significant difference between patients carrying mutations in exon 2 (n = 24,46.83, 8.31) and exon 4 (n = 18, 37.75, 7.67) (p = 0.002). The median (IQR) diagnostic delay from symptom onset was 14.50 (6.00–36.50) months for all SOD1-mutant patients, 9.50 (4.75–24.25) months for males and 24.00 (9.50–47.50) months for females, revealing a gender difference (p = 0.009). Similar advantages in median (IQR) ΔFS [male: female, 0.55 (0.24–0.94) vs 0.19 (0.06–0.90), p = 0.041] and mean (95% CI) survival [57.4 (38.90–75.90) months vs 125.6 (99.80–151.50) months, p = 0.006] were also observed in females, both of which existed in sporadic ALS only when stratified by familiar or sporadic ALS. Conclusions The results highlight a distinct mutational distribution and natural history spectrum in ALS patients carrying SOD1 mutations in China. A prominent mild disease progression was observed in female patients, which had rarely been reported in the previous literature. This finding, together with the detailed analysis of natural history among each mutation, can have important implications for future genetic counselling and SOD1-targeted clinical trials. |
| first_indexed | 2024-12-19T20:35:49Z |
| format | Article |
| id | doaj.art-759feff7ed27464fa9e8a4fa794709fb |
| institution | Directory Open Access Journal |
| issn | 2047-9158 |
| language | English |
| last_indexed | 2024-12-19T20:35:49Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Neurodegeneration |
| spelling | doaj.art-759feff7ed27464fa9e8a4fa794709fb2022-12-21T20:06:33ZengBMCTranslational Neurodegeneration2047-91582019-01-018111010.1186/s40035-018-0142-8Better survival in female SOD1-mutant patients with ALS: a study of SOD1-related natural historyLu Tang0Yan Ma1Xiao-lu Liu2Lu Chen3Dong-sheng Fan4Department of Neurology, Peking University Third HospitalDepartment of Neurology, Peking University Third HospitalDepartment of Neurology, Peking University Third HospitalDepartment of Neurology, Peking University Third HospitalDepartment of Neurology, Peking University Third HospitalAbstract Background SOD1 mutations are the most common cause of amyotrophic lateral sclerosis (ALS) in non-Caucasian patients. Detailed natural history profiles of SOD1-mutant patients will be beneficial for the strategy and interpretation of future SOD1-targeted clinical practice. Methods Mutational distribution, age at onset (AAO), site of onset, diagnostic delay, disease progression (rate of ALSFRS-R decrease, ΔFS) and survival were analysed. Further comparisons between heredity of disease, gender, and mutations were performed. Results Sixty-six cases with 43 SOD1 mutations were included and analysed, with p.His47Arg as the leading mutation and seven novel variants identified. The mean (SD) AAO was 43.92 years (9.24) for all subjects, with a significant difference between patients carrying mutations in exon 2 (n = 24,46.83, 8.31) and exon 4 (n = 18, 37.75, 7.67) (p = 0.002). The median (IQR) diagnostic delay from symptom onset was 14.50 (6.00–36.50) months for all SOD1-mutant patients, 9.50 (4.75–24.25) months for males and 24.00 (9.50–47.50) months for females, revealing a gender difference (p = 0.009). Similar advantages in median (IQR) ΔFS [male: female, 0.55 (0.24–0.94) vs 0.19 (0.06–0.90), p = 0.041] and mean (95% CI) survival [57.4 (38.90–75.90) months vs 125.6 (99.80–151.50) months, p = 0.006] were also observed in females, both of which existed in sporadic ALS only when stratified by familiar or sporadic ALS. Conclusions The results highlight a distinct mutational distribution and natural history spectrum in ALS patients carrying SOD1 mutations in China. A prominent mild disease progression was observed in female patients, which had rarely been reported in the previous literature. This finding, together with the detailed analysis of natural history among each mutation, can have important implications for future genetic counselling and SOD1-targeted clinical trials.http://link.springer.com/article/10.1186/s40035-018-0142-8Amyotrophic lateral sclerosisNatural history studiesSOD1 mutationsGender difference |
| spellingShingle | Lu Tang Yan Ma Xiao-lu Liu Lu Chen Dong-sheng Fan Better survival in female SOD1-mutant patients with ALS: a study of SOD1-related natural history Translational Neurodegeneration Amyotrophic lateral sclerosis Natural history studies SOD1 mutations Gender difference |
| title | Better survival in female SOD1-mutant patients with ALS: a study of SOD1-related natural history |
| title_full | Better survival in female SOD1-mutant patients with ALS: a study of SOD1-related natural history |
| title_fullStr | Better survival in female SOD1-mutant patients with ALS: a study of SOD1-related natural history |
| title_full_unstemmed | Better survival in female SOD1-mutant patients with ALS: a study of SOD1-related natural history |
| title_short | Better survival in female SOD1-mutant patients with ALS: a study of SOD1-related natural history |
| title_sort | better survival in female sod1 mutant patients with als a study of sod1 related natural history |
| topic | Amyotrophic lateral sclerosis Natural history studies SOD1 mutations Gender difference |
| url | http://link.springer.com/article/10.1186/s40035-018-0142-8 |
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