High frequency of the TARDBP p.M337 V mutation among south-eastern Chinese patients with familial amyotrophic lateral sclerosis
| Autor: | Ling-Ling Zhan, Liu-Qing Xu, Min-Ting Lin, Wan-Jin Chen, Wei Hu, Chong Wang, Qi-Jie Zhang, Ning Wang, Guo-Rong Xu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology China medicine.medical_specialty DNA Mutational Analysis Single-nucleotide polymorphism TARDBP lcsh:RC346-429 03 medical and health sciences symbols.namesake Exon 0302 clinical medicine Familial Asian People Internal medicine Humans Medicine Amyotrophic lateral sclerosis lcsh:Neurology. Diseases of the nervous system Sanger sequencing Genotype-phenotype analysis business.industry Genetic heterogeneity General Medicine Middle Aged medicine.disease DNA-Binding Proteins 030104 developmental biology Mutation Mutation (genetic algorithm) symbols Neurology (clinical) Age of onset business 030217 neurology & neurosurgery Research Article |
| Zdroj: | BMC Neurology, Vol 18, Iss 1, Pp 1-6 (2018) BMC Neurology |
| ISSN: | 1471-2377 |
| DOI: | 10.1186/s12883-018-1028-1 |
| Popis: | Background Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease characterized by substantial clinical and genetic heterogeneity. Thus far, only a few TARDBP-ALS families have been reported in China, and no mutation analysis has been reported in south-eastern China. Methods Seven index cases from ALS families negative for SOD1 and FUS mutations were screened by Sanger sequencing for TARDBP gene exons 2-6. TARDBP exon 6 was analysed in 215 sporadic ALS patients. Results Two TARDBP mutations in exon 6 (p.M337 V and p.G348C) were identified in 5 unrelated families. Four of these 5 families carried the same p.M337 V mutation (family 1II3, family 2II6, family 3II4, and family 4II4), and the p.G348C mutation was identified in family 5 (II5). Among the 215 sporadic patients, only a single nucleotide polymorphism (p.A366A) was detected in 5 patients, and no responsible mutation was identified. Among the TARDBP-linked familial ALS patients, the average age of onset was 57.0 ± 4.7 years, and a trend towards higher rates of bulbar (50.0%, 6/12) onset and upper limb (41.7%, 5/12) onset than lower rates of limb onset (8.3%, 1/12) was observed. Furthermore, ALS patients with TARDBP mutations showed a benign disease course, and the average survival was 106.5 ± 41.8 months (n = 8). Conclusions We found a high frequency of the TARDBP p.M337 V mutation in familial ALS in south-eastern China. The TARDBP-linked ALS patients showed a benign disease course and prolonged survival. Electronic supplementary material The online version of this article (10.1186/s12883-018-1028-1) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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