Dataset Information

ANXA11 mutations prevail in Chinese ALS patients with and without cognitive dementia.

ABSTRACT:

Objective

To investigate the genetic contribution of ANXA11, a gene associated with amyotrophic lateral sclerosis (ALS), in Chinese ALS patients with and without cognitive dementia.

Methods

Sequencing all the coding exons of ANXA11 and intron-exon boundaries in 18 familial amyotrophic lateral sclerosis (FALS), 353 unrelated sporadic amyotrophic lateral sclerosis (SALS), and 12 Chinese patients with ALS-frontotemporal lobar dementia (ALS-FTD). The transcripts in peripheral blood generated from a splicing mutation were examined by reverse transcriptase PCR.

Results

We identified 6 nonsynonymous heterozygous mutations (5 novel and 1 recurrent), 1 splice site mutation, and 1 deletion of 10 amino acids (not accounted in the mutant frequency) in 11 unrelated patients, accounting for a mutant frequency of 5.6% (1/18) in FALS, 2.3% (8/353) in SALS, and 8.3% (1/12) in ALS-FTD. The deletion of 10 amino acids was detected in 1 clinically undetermined male with an ALS family history who had atrophy in hand muscles and myotonic discharges revealed by EMG. The novel p. P36R mutation was identified in 1 FALS index, 1 patient with SALS, and 1 ALS-FTD. The splicing mutation (c.174-2A>G) caused in-frame skipping of the entire exon 6. The rest missense mutations including p.D40G, p.V128M, p.S229R, p.R302C and p.G491R were found in 6 unrelated patients with SALS.

Conclusions

The ANXA11 gene is one of the most frequently mutated genes in Chinese patients with SALS. A canonical splice site mutation leading to skipping of the entire exon 6 further supports the loss-of-function mechanism. In addition, the study findings further expand the ANXA11 phenotype, first highlighting its pathogenic role in ALS-FTD.

SUBMITTER: Zhang K

PROVIDER: S-EPMC5963931 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Publications

<i>ANXA11</i> mutations prevail in Chinese ALS patients with and without cognitive dementia.

Zhang Kang K Liu Qing Q Liu Keqiang K Shen Dongchao D Tai Hongfei H Shu Shi S Ding Qingyun Q Fu Hanhui H Liu Shuangwu S Wang Zhili Z Li Xiaoguang X Liu Mingsheng M Zhang Xue X Cui Liying L

Neurology. Genetics 20180522 3

<h4>Objective</h4>To investigate the genetic contribution of <i>ANXA11</i>, a gene associated with amyotrophic lateral sclerosis (ALS), in Chinese ALS patients with and without cognitive dementia.<h4>Methods</h4>Sequencing all the coding exons of <i>ANXA11</i> and intron-exon boundaries in 18 familial amyotrophic lateral sclerosis (FALS), 353 unrelated sporadic amyotrophic lateral sclerosis (SALS), and 12 Chinese patients with ALS-frontotemporal lobar dementia (ALS-FTD). The transcripts in perip ...[more]

PMID: 29845112

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