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

作者：Sun, Yi-min; Dong, Yi; Wang, Jian; Lu, Jia-hong; Chen, Yan^*; Wu, Jian-jun^*

来源：Journal of Neurology, 2017, 264(12): 2387-2393.

DOI：10.1007/s00415-017-8628-3

• Vesicle-associated membrane protein-associated protein B
• Amyotrophic lateral sclerosis
• Chinese
• Mutation

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.

• 出版日期2017-12
• 单位复旦大学