High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients
Braz. j. med. biol. res
;
39(9): 1171-1179, Sept. 2006. tab
Artículo
en Inglés
| LILACS
| ID: lil-435430
ABSTRACT
Gaucher disease (GD), the most prevalent lysosome storage disorder, presents an autosomal recessive mode of inheritance. It is a paradigm for therapeutic intervention in medical genetics due to the existence of effective enzyme replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian patients, carried out in order to establish the frequency of the most common mutations and to provide prognostic information based on genotype-phenotype correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47 percent of all the alleles, but N370S/N370S homozygosity was found in only 10 percent of the patients, a much lower frequency than expected, suggesting that most individuals presenting this genotype may not receive medical attention. Recombinant alleles were detected at a high frequency: 44 percent of the chromosomes bearing mutation L444P had other mutations derived from the pseudogene sequence, present in 25 percent of patients. Three neuronopathic type 2 patients were homozygous for L444P, all presenting additional mutations (E326K or recombinant alleles) that probably lead to the more severe phenotypes. Six children, classified as type 1 GD patients, had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest later in life. This would indicate the need for a higher treatment dose during enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous type 1 patients and also in compound heterozygosity in 5 (42 percent) type 3 patients. These findings indicate that G377S cannot be unambiguously classified as mild and suggest an allele-dose effect for this mutation.
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Índice:
LILACS (Américas)
Asunto principal:
Análisis Mutacional de ADN
/
Alelos
/
Enfermedad de Gaucher
/
Mutación
Tipo de estudio:
Estudio diagnóstico
/
Estudio pronóstico
Límite:
Humanos
País/Región como asunto:
America del Sur
/
Brasil
Idioma:
Inglés
Revista:
Braz. j. med. biol. res
Asunto de la revista:
Biologia
/
Medicina
Año:
2006
Tipo del documento:
Artículo
País de afiliación:
Brasil
Institución/País de afiliación:
Hospital Evangélico de Londrina/BR
/
Hospital de Base do Distrito Federal/BR
/
Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti/BR
/
Santa Casa de São Paulo/BR
/
Universidade Federal do Estado de São Paulo/BR
/
Universidade de São Paulo/BR
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