Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. Missense mutations of DCTN1 have been identified as a possible genetic risk factor for ALS. Here, we tested the DCTN1 protein-coding exons in 510 sporadic ALS patients in whom SOD1, TARDBP, FUS, and C9orf72 genes were screened before. Polymerase chain reaction and Sanger sequencing were used for mutation discovery. The results revealed two rare heterozygous missense variants, c.1867C>T (p.R623W) and c.2798C>T (p.A933V). These two patients exhibited spinal disease onset without cognitive impairment, and their onset age and diagnosis delay was within the average range of Chinese ALS patients. Our results suggested that variants in DCTN1 are not common risk factors for Chinese sporadic ALS and that the frequency of variants of unknown significance in the cohort study was 0.39%.
Highlights
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the selective impairment of the motor cortex and motor neurons of the brainstem and the spinal cord
14 variants were considered benign polymorphisms, because they were synonymous or have been identified in Exome Variant Server (EVS), the Genomes Project (TGP) or Exome Aggregation Consortium (ExAC) database
These two variants were not present in the 490 race-matched control or population based databases (EVS, dbSNP, 1000 Genomes Project, and ExAC, including more than 65,000 individuals, >4,300 East Asian population) and both located in a highly-conserved region
Summary
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the selective impairment of the motor cortex and motor neurons of the brainstem and the spinal cord. DCTN1 is not a common genetic cause in familial cases, the mutation frequencies in sporadic ALS vary from 0.51% to 2.87% in different populations [6,7,8,9]. The dynactin complex acts as a connector of cargos with microtubules and cytoplasmic dynein in the process of retrograde vesicle transport, which is involved in centripetal movement of lysosomes and endosomes, ER-to-Golgi transport, spindle formation, chromosome movement, nuclear positioning, and axonogenesis[5, 13]. Disturbing this interaction influences fast axonal transport and disrupts physiologic neuronal function[11]. DCTN1 was first sequenced in a large Chinese population with sporadic ALS, and we wanted to investigate the mutation frequencies and spectrum in DCTN1
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
