title: Alanyl-tRNA synthetase mutation in a family with dominant distal hereditary motor neuropathy.
abstract: OBJECTIVE
  To identify a new genetic cause of distal hereditary motor neuropathy (dHMN), which is also known as a variant of Charcot-Marie-Tooth disease (CMT), in a Chinese family.
  
  
  METHODS
  We investigated a Chinese family with dHMN clinically, electrophysiologically, and genetically. We screened for the mutations of 28 CMT or related pathogenic genes using an originally designed microarray resequencing DNA chip.
  
  
  RESULTS
  Investigation of the family history revealed an autosomal dominant transmission pattern. The clinical features of the family included mild weakness and wasting of the distal muscles of the lower limb and foot deformity, without clinical sensory involvement. Electrophysiologic studies revealed motor neuropathy. MRI of the lower limbs showed accentuated fatty infiltration of the gastrocnemius and vastus lateralis muscles. All 4 affected family members had a heterozygous missense mutation c.2677G>A (p.D893N) of alanyl-tRNA synthetase (AARS), which was not found in the 4 unaffected members and control subjects.
  
  
  CONCLUSIONS
  An AARS mutation caused dHMN in a Chinese family. AARS mutations result in not only a CMT phenotype but also a dHMN phenotype.
authors.affiliation: Departments of Neuromuscular Disease, Third Hospital of Hebei Medical University, Shijiazhuang, PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhao
authors.forename: A
authors.initials: A
authors.lastname: Hashiguchi
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.forename: Y
authors.initials: Y
authors.lastname: Sakiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Okamoto
authors.forename: S
authors.initials: S
authors.lastname: Tokunaga
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: H
authors.initials: H
authors.lastname: Takashima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000412:Alanine-tRNA Ligase / Q000235:genetics*; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020125:Mutation, Missense
chemical_list: D000412:Alanine-tRNA Ligase