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Identification of a Missense Mutation in the α-galactosidase A Gene in a Chinese Family with Fabry Disease

[ Vol. 19 , Issue. 1 ]

Author(s):

Yuan Wu , Hong Xia, Jinzhong Yuan , Hongbo Xu, Xiong Deng, Jun Liu, Hao Zhang and Hao Deng*   Pages 70 - 75 ( 6 )

Abstract:


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.

Keywords:

Fabry disease, α-galactosidase A, Phenotype, The GLA gene, Mutation, p.G261V.

Affiliation:

Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013, Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013, Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013, Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013, Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha 410013, Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha 410013

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