title: A Novel Missense Mutation of theDDHD1Gene Associated with Juvenile Amyotrophic Lateral Sclerosis.
abstract: Background:Juvenile amyotrophic lateral sclerosis (jALS) is a rare form of ALS with an onset age of less than 25 years and is frequently thought to be genetic in origin.DDHD1gene mutations have been reported to be associated with the SPG28 subtype of autosomal recessive HSP but have never been reported in jALS patients.Methods:Gene screens for the causative genes of ALS, HSP and CMT using next-generation sequencing (NGS) technologies were performed on a jALS patient. Sanger sequencing was used to validate identified variants and perform segregation analysis.Results:We identified a novel c.1483A>G (p.Met495Val) homozygous missense mutation of theDDHD1gene in the jALS patient. All of his parents and young bother were heterozygous for this mutation. The mutation was not found in 800 Chinese control subjects or the database of dbSNP, ExAC and 1000G.Conclusion:The novel c.1483A>G (p.Met495Val) missense mutation of theDDHD1gene could be a causative mutation of autosomal recessive jALS.
authors.affiliation: Department of Neurology, Peking University Third Hospital Beijing, China.
authors.forename: Chujun
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Neurology, Peking University Third Hospital Beijing, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Fan
keywords: DDHD1 gene; amyotrophic lateral sclerosis; hereditary spastic paraplegia; juvenile; mutation