Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results from the deficient activity of the lysosomal exoglycohydrolase, alpha-galactosidase A (EC 3.2.1.22; 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.

作者：G A, Ashley；J, Shabbeer；M, Yasuda；C M, Eng；R J, Desnick

来源：Journal of human genetics 2001 年 46卷 4期