Amissense Mutationof The α-galactosidase A Geneina Chinese Familyof Fabry Disease With Renal Failure

Objective：To investigate a Chinese family diagnosed with Fabry disease, and explore theeffect of genotype on phenotype.Methods：Clinical data of the proband and his family members was obtained, and theperipheral blood of the proband, his sister and a normal control was collected. GenomicDNA was isolated from the whole blood, and seven exons of the α-gal A gene wasamplifed by polymerase chain reaction (PCR) with six sets of primers. The DNA segmentswere purified and sequenced. In addition, the plasma α-gal A activity analysis was alsoperformed.Results: The α-gal A activity of the proband in this family was0.03nmol/ml/h in theplasma. PCR amplification and sequencing of the α-gal A gene exons revealed a singleC-to-T transition in codon112of exon2. This transition, mapping to position334in thecDNA of the α-gal A gene, was a missense mutation predicting an arginine to cysteinesubstitution (p.R112C), thus altering the normal activity of α-gal A enzyme. No mutationswere detected in the other six exons of the α-galAgene.Conclusion: The present results strongly demonstrated that the missense mutation, p.R112C, in α-gal Agene induced the activity deletion and FD development correlated withrenal damage.