title: A novel mutation of α-galactosidase A gene causes Fabry disease mimicking primary erythromelalgia in a Chinese family.
abstract: OBJECTIVE
  Fabry disease is an X-linked genetic disorder caused by the mutations of α-galactosidase A (GLA, MIM 300644) gene presenting with various clinical symptoms including small-fiber peripheral neuropathy and limb burning pain. Here, we reported a Chinese pedigree with the initial diagnosis of primary erythromelalgia in an autosomal dominant (AD)-inherited pattern.
  
  
  METHODS
  Mutation analysis of SCN9A and GLA genes by direct sequencing and functional analysis of a novel mutation of GLA in cells were performed.
  
  
  RESULTS
  Our data did not show any pathological mutations in SCN9A gene; however, a novel missense mutation c.139T>C (p.W47R) of GLA was identified in a male proband as well as two female carriers in this family. Enzyme assay of α-galactosidase A activity showed deficient enzyme activity in male patients and female carriers, further confirming the diagnosis of Fabry disease. Finally, a functional analysis indicated that the replacement of the 47th amino acid tryptophan (W47) with arginine (W47R) or glycine (W47G) led to reduced activity of α-galactosidase A in 293T cells. Therefore, these findings demonstrated that the novel mutation p.W47R of GLA is the cause of Fabry disease.
  
  
  CONCLUSIONS
  Because Fabry disease and primary erythromelalgia share similar symptoms, it is a good strategy for clinical physicians to perform genetic mutation screenings on both SCN9A and GLA genes in those patients with limb burning pain but without a clear inheritant pattern.
authors.affiliation: a Department of Neurology , The Second Affiliated Hospital of Soochow University , Suzhou , China.|f Department of Neurology , The Affiliated Hospital of Xuzhou Medical College , Xuzhou , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
authors.affiliation: b Institute for Fetology , The First Affiliated Hospital of Soochow University , Suzhou , China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wei
authors.affiliation: c Institute of Neuroscience , Soochow University , Suzhou , China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.affiliation: c Institute of Neuroscience , Soochow University , Suzhou , China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Miao
authors.affiliation: d Laboratory of Clinical Genetics , Peking Union Medical College Hospital , Beijing , China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Zhang
authors.affiliation: a Department of Neurology , The Second Affiliated Hospital of Soochow University , Suzhou , China.
authors.forename: Cuihua
authors.initials: C
authors.lastname: Leng
authors.affiliation: e Department of Neurology , Suzhou Kowloon Hospital , Suzhou , China.
authors.forename: Jizhen
authors.initials: J
authors.lastname: Li
authors.affiliation: a Department of Neurology , The Second Affiliated Hospital of Soochow University , Suzhou , China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: b Institute for Fetology , The First Affiliated Hospital of Soochow University , Suzhou , China.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.affiliation: a Department of Neurology , The Second Affiliated Hospital of Soochow University , Suzhou , China.|c Institute of Neuroscience , Soochow University , Suzhou , China.
authors.forename: Xingshun
authors.initials: X
authors.lastname: Xu
mesh_terms: D002681:China; D004252:DNA Mutational Analysis; D004916:Erythromelalgia / Q000503:physiopathology*; D000795:Fabry Disease / Q000235:genetics*; D005192:Family Health; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D014162:Transfection; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D000519:alpha-Galactosidase
keywords: Fabry disease; mutation; primary erythromelalgia; α-galactosidase A