Background: Fabry disease results from a genetic deficiency of alpha-galactosidase A (GLA) activity. Phenotype-genotype correlations in this condition have not as yet been fully elucidated.
Objective: To report a case of a male patient with classical Fabry disease and his mother, a heterozygous female with Fabry disease, showing cardiac involvement, and to identify the underlying GLA gene mutation in this particular phenotype.
Patients/methods: Genomic DNA was extracted from the patient, his mother and the unaffected family members. Biopsy specimens of skin, heart and kidney were examined using light and electron microscopy. The mutation was identified by polymerase chain reaction and direct sequencing and was confirmed by restriction enzyme fragment length polymorphism.
Results: The G-->C transversion was identified in codon 97 of the GLA gene and resulted in an A97P amino acid substitution that was a novel pathogenic GLA gene mutation. The male patient who had classical Fabry disease was hemizygous and his mother was heterozygous for this mutation.
Conclusions: These results indicate that the A97P amino acid substitution in GLA might tend to induce classical Fabry disease.