title: [Genetic and clinical study of three Chinese pedigrees with Fabry disease].
abstract: OBJECTIVE
  Fabry disease is a rare lysosome storage disease featuring X-linked recessive inheritance. The study was to explore potential mutations of alpha-galactosidase A (GLA) gene and their correlation with clinic manifestations in three Chinese pedigrees with Fabry disease.
  
  
  METHODS
  All exons and flanking sequences of GLA gene were amplified with PCR. Potential mutations were detected with bidirectional DNA sequencing. Correlation between particular mutations and clinic features were analyzed.
  
  
  RESULTS
  A unreported missense mutation, c.797A>C (D266A) in GLA exon 5 was identified in pedigree 1. Also in exon 5, a missense mutation c.644A>G (N215S) was found in pedigree 2. In pedigree 3, a nonsense mutation c.355C>T (Q119X) was found in exon 2. The c.797A>C mutation was not detected in 200 unrelated male controls. The probands of pedigrees 1 and 3 had presented mainly with skin damage and chronic renal insufficiency, whilst the proband of pedigree 2 had presented with hypertrophic cardiomyopathy.
  
  
  CONCLUSIONS
  The unreported c.797A>C (D266A) mutation is the sixth missense type mutation of the 266th codon of GLA gene, and all other 5 missense mutations reported previously had been confirmed to be responsible for Fabry disease. The c.797A>C mutation, not found in 200 unrelated male controls, may be the causative mutation in pedigree 1. The c.644A>G and c.355C>T mutations were first detected in Chinese patients. Variable phenotypes of Fabry disease may be in part attributed to the natures of particular mutations of GLA gene.
authors.affiliation: Department of Nephrology, West China Hospital, Sichuan University, P.R. China.
authors.forename: Mao-lu
authors.initials: ML
authors.lastname: Tian
authors.forename: Yuan-long
authors.initials: YL
authors.lastname: Yan
authors.forename: Jia-chuan
authors.initials: JC
authors.lastname: Xiong
authors.forename: Xiao-xia
authors.initials: XX
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhang-xue
authors.initials: ZX
authors.lastname: Hu
mesh_terms: D000328:Adult; D000795:Fabry Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D000519:alpha-Galactosidase / Q000235:genetics*
chemical_list: D000519:alpha-Galactosidase