Genotype: A Crucial but Not Unique Factor Affecting the Clinical Phenotypes in Fabry Disease

PLoS One. 2016 Aug 25;11(8):e0161330. doi: 10.1371/journal.pone.0161330. eCollection 2016.


Numerous α-galactosidase A (α-gal A) gene (GLA) mutations have been identified in Fabry disease (FD), but studies on genotype-phenotype correlation are limited. This study evaluated the features of GLA gene mutations and genotype-phenotype relationship in Chinese FD patients. Gene sequencing results, demographic information, clinical history, and laboratory findings were collected from 73 Chinese FD patients. Totally 47 mutations were identified, including 23 novel mutations which might be pathogenic. For male patients, those with frameshift and nonsense mutations presented the classical FD, whereas those with missense mutations presented both of classical and atypical phenotypes. Interestingly, two male patients with missense mutation p.R356G from two unrelated families, and two with p.R301Q from one family presented different phenotypes. A statistically significant association was found between the levels of α-gal A enzyme activity and ocular changes in males, though no significant association was found between residual enzyme activity level and genotype or clinical phenotypes. For female patients, six out of seven with frameshift mutations and one out of nine with missense mutation presented the classical FD, and α-gal A activity in those patients was found to be significantly lower than that of patients with atypical phenotypes (13.73 vs. 46.32 nmol/ml/h/mg). Our findings suggest that the α-gal A activity might be associated with the clinical severity in female patients with FD. But no obvious associations between activity level of α-gal A and genotype or clinical phenotypes were found for male patients.

MeSH terms

  • Adult
  • Asian Continental Ancestry Group / genetics
  • China
  • Codon, Nonsense
  • Fabry Disease / diagnosis*
  • Fabry Disease / genetics*
  • Female
  • Frameshift Mutation
  • Genetic Association Studies*
  • Genotype
  • Humans
  • Male
  • Mutation*
  • Mutation, Missense
  • Phenotype
  • Sequence Analysis, DNA
  • Young Adult
  • alpha-Galactosidase / metabolism


  • Codon, Nonsense
  • alpha-Galactosidase

Grant support

NC is supported by the national Basic Research Program of China 973 No. 2012CB517600 (No. 2012CB517604, []) and Key Program of Shanghai Science and Technology Commission (No.08dz1900502, []). XP is sponsored by the National Natural Science Foundation of China (No.30871001, []). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.