Browsing by Author "Khowsathit, Pongsakdi"
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Item Clinical and molecular characterization of an extended family with Fabry disease.(2006-09-15) Wattanasirichaigoon, Duangrurdee; Svasti, Jisnuson; Cairns, James R Ketudat; Tangnararatchakit, Kanchana; Visudtibhan, Anannit; Keeratichamroen, Siriporn; Ngiwsara, Lukana; Khowsathit, Pongsakdi; Onkoksoong, Tassanee; Lekskul, Apatsa; Mongkolsiri, Dowruang; Jariengprasert, Chanchai; Thawil, Cheamchit; Ruencharoen, SuwimolOBJECTIVE: To characterize clinical manifestations, biochemical changes, mutation of alpha-Galactosidase (alpha-Gal A) gene A (GLA), and functional capability of mutant protein. MATERIAL AND METHOD: Seventeen subjects from a family with a newly diagnosed patient with Fabry disease were enrolled in the present study. In each individual, clinical history, physical examination, leukocyte enzyme activity of alpha-Gal A, and mutation analysis were performed. Those with a mutation were further investigated by ophthalmological and audiological evaluations, electrocardiography, echocardiogram, urinalysis, and blood tests to determine renal insufficiency. Expression study of the mutant protein was performed using a Pichia pastoris expression system. RESULTS: Four affected males and five symptomatic female carriers were identified. Clinical manifestations included severe neuropathic pain, acroparesthesia, hypo-/hyper-hidrosis, frequent syncope, ischemic stroke, cardiac hypertrophy, corneal dystrophy and cart-wheel cataract, high frequency sensorineural hearing loss, periorbital edema and subcutaneous edema over hands and interphalangeal joints. None had angiokeratoma or renal symptoms. The authors identified a novel mutation, p.L106R, in the GLA gene. Recombinant expression of the mutant protein gave little or no enzyme activity compared to the normal protein. CONCLUSION: There were intrafamilial clinical variabilities, but consistent findings of the absence of angiokeratoma and renal symptoms, which could represent a unique feature of this particular mutation.