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A novel mutation of VAPB in one Chinese familial amyotrophic lateral sclerosis pedigree and its clinical characteristics

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Abstract

The mutation of vesicle-associated membrane protein-associated protein B (VAPB) was proved to cause family amyotrophic lateral sclerosis (FALS). Only two mutations of VAPB associated with ALS have been reported (p.Pro56Ser and p.Thr46Ile). Here we reported a Chinese Han FALS family caused by a novel VAPB point mutation. The clinical materials of one Chinese Han FALS family were collected. The genetic analysis was carried out by target sequencing and further verified by Sanger sequencing. One novel mutation of c.167C>A (p.Pro56His) on VAPB was found in the proband. The age at onset of the proband was 48 with the onset symptoms of weakness in the right arm, followed by progressive limb and trunk weakness with decreased deep-tendon reflexes, muscular cramps and fasciculation. But the disease duration was more than 15 years. He was under the tracheotomy for 1 year at last visit. Electromyography showed widespread acute and chronic neurogenic damages. His mother presented weakness in her limbs in 50 s and died 15 years later. One of his younger sisters diagnosed as ALS for 6 years also carried the same mutation. She presented the similar symptoms on 41. No dominant upper motor neuron sign was showed. The clinical features were similar to the patients carrying the known mutation of p.Pro56Ser. A novel mutation of VAPB was found in one Chinese Han FALS pedigree. The affected patients presented a much slower progression and the lesions were limited in lower motor neurons.

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Acknowledgements

This study was supported by the Founding of Shanghai Municipal Commission of Health and Family Planning (20124222).

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  1. Yi-min Sun and Yi Dong contributed equally to the work.

Authors and Affiliations

  1. Department of Neurology, National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China

    Yi-min Sun, Yi Dong, Jian Wang, Jia-hong Lu, Yan Chen & Jian-jun Wu

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  1. Yi-min Sun
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  2. Yi Dong
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  4. Jia-hong Lu
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Correspondence to Yan Chen or Jian-jun Wu.

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This study has been approved by the ethics committee of Huashan hospital and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Sun, Ym., Dong, Y., Wang, J. et al. A novel mutation of VAPB in one Chinese familial amyotrophic lateral sclerosis pedigree and its clinical characteristics. J Neurol 264, 2387–2393 (2017). https://doi.org/10.1007/s00415-017-8628-3

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  • DOI: https://doi.org/10.1007/s00415-017-8628-3

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