á-Galactosidase A gene mutations detected in Fabry patients from Argentina

ROZENFELD PA; FOSSATI CA

Valencia, España

Simposio; 5th International Symposium on Lysosomal Storage Diseases; 2005

Shire HGT

a-GALACTOSIDASE A GENE MUTATIONS DETECTED IN FABRY PATIENTS FROM ARGENTINA   ROZENFELD PAULA, FOSSATI CARLOS. Cátedra de Inmunología, Universidad Nacional de La Plata. Argentina   INTRODUCCION: Fabry disease is diagnosed by the decreased levels of a-galactosidase A (a-gal A) activity. In males, enzymatic activity determination in blood is reliable, although in heterozygous females, is often inconclusive. Only, identification of a mutation in a-gal A gene provide the precise heterozygote identification. AIM: To describe 4 mutations found in 4 unrelated families with Fabry disease from Argentina. METHODS: Blood samples were collected in filter paper. The filter paper s were cut, washed and air-dried, and used as a template for PCR amplification of the 7 exons and adjacent intron-exon boundaries of a-gal A gene. After purification of the amplicons, they were sequenced. RESULTS: Mutation 1 is a G-to-C transversion in position 463 of exon 3, leading to a change from aspartate to histidine in aminoacid 155 (D155H). Mutation 2 is a T-to-C transition in position 1244 of exon 7, resulting in the replacement of the 415 leucine to a proline (L415P). Mutations 3 is a T-to-G transversion, changing aminoacid 243 from leucine to tryptophan (L243W). Mutation 4 is a G-to A transition in position 281, causing the change of the cysteine 94 to a tyrosine (C94Y). CONCLUSIONS: We detected 4 missense mutations in a-gal A gene from Fabry patients of Argentina. Mutation 1 changes an acidic aminoacid to a basic one, mutation 2 introduces a proline that is known to alters the polypeptide structure, mutation 3 changes a leucin to triptophane and mutation 4 disrupts a disulfide bond of the protein. As our knowledge, mutations 1 to 3 are novel mutations leading to Fabry disease, and number 4 was already described.