Clinical and molecular characterization of an extended family with Fabry disease.
Artigo
em Inglês
| IMSEAR
| ID: sea-44214
ABSTRACT
OBJECTIVE:
To characterize clinical manifestations, biochemical changes, mutation of alpha-Galactosidase (alpha-Gal A) gene A (GLA), and functional capability of mutant protein. MATERIAL ANDMETHOD:
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.
Texto completo:
DisponíveL
Índice:
IMSEAR (Sudeste Asiático)
Assunto principal:
Linhagem
/
Idoso
/
Feminino
/
Humanos
/
Masculino
/
Análise Mutacional de DNA
/
Família
/
Criança
/
Pré-Escolar
/
Adolescente
Tipo de estudo:
Estudo prognóstico
Idioma:
Inglês
Ano de publicação:
2006
Tipo de documento:
Artigo
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