Introduction: Fabry Disease (FD), the second most common lysosomal storage disorder
after Gaucher disease, is characterized by variable clinical manifestations, including angiokeratoma,
corneal dystrophy, recurrent episodes of extremity pain, renal impairment, cardiac complications and
cerebrovascular manifestations. It is caused by mutations in the α-galactosidase A gene (gene symbol
GLA) on chromosome Xq22, which leads to deficiency of lysosomal α-galactosidase A (α-Gal A), and
subsequent accumulation of glycosphingolipids in various tissues and organs. The aim of this study is
to identify the disease-causing mutation in a five-generation Chinese family with FD. A c.782G>T
transversion (p.G261V) in the GLA gene was identified in four patients and two asymptomatic carriers
by direct sequencing, and it co-segregated with the disease in the family. The variant is predicted to be
disease-causing mutation and result in seriously abnormal function of α-Gal A. Four patients in this
family present with classic phenotype of FD, including acroparesthesias, hypohidrosis, angiokeratomas
and intermittent burning pain in extremity.
Conclusion: The disease severity is similar among male and female patients. Our study extends the
genotype-phenotype relationship between mutations in the GLA gene and clinical findings of FD,
which may be helpful in the genetic counseling of patients with FD.