Fabry disease: twenty novel alpha-galactosidase A mutations causing the classical phenotype

J Hum Genet. 2001;46(4):192-6. doi: 10.1007/s100380170088.


Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results from the deficient activity of the lysosomal exoglycohydrolase, alpha-galactosidase A (EC; alpha-Gal A). The nature of the molecular lesions in the alpha-Gal A gene in 40 unrelated families with the classical phenotype (absent alpha-Gal A activity) was determined in order to provide precise heterozygote detection and prenatal diagnosis, and to explore possible genotype/phenotype correlations. Genomic DNA was isolated from unrelated affected males, and the entire alpha-Gal A coding region and flanking intronic sequences were analyzed by polymerase chain reaction (PCR) amplification and automated sequencing. Twenty new mutations were identified: M51K, D92N, D136H, F169S, C172F, L191Q, S247P, Q250X, P259R, G261D, T282N, R301P, W349X, T410K, 124delAT, 842delTAA, 1033delTC, 82insG, 893insG, and 903insG. In the remaining 20 unrelated Fabry families, 17 previously reported mutations were detected. These studies further define the heterogeneity of mutations in the alpha-Gal A gene causing the classic Fabry disease phenotype, and permit precise heterozygote detection and prenatal diagnosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • DNA Mutational Analysis
  • Fabry Disease / genetics*
  • Family Health
  • Genotype
  • Humans
  • Male
  • Mutation
  • Phenotype
  • alpha-Galactosidase / genetics*


  • alpha-Galactosidase