Mutation analysis and genotype/phenotype relationships of Gaucher disease patients in Spain

Alfonso, Pilar; Aznarez, Sofía; Giralt, Manuel; Pocovı́, Miguel; Giraldo, Pilar

doi:10.1007/s10038-007-0135-4

Cited by 55 publications

(34 citation statements)

References 14 publications

(15 reference statements)

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“…After screening for the most frequent alleles, only 21% of the disease-related alleles remained unidentified in our patients, indicating an intermediate frequency of sporadic, unknown mutations, different from both reference populations. The prevalence of the N370S mutation (around 56%) is one of the highest in Europe, comparable only to that reported in Spanish GD patients (50%) (20). The low frequency of the L444P substitution (around 16%) is also comparable to that of the Spanish popBrought to you by | MIT Libraries Authenticated Download Date | 5/9/18 9:06 AM ratories, including ours.…”

Section: Discussionsupporting

confidence: 56%

Laboratory diagnosis and follow-up of Romanian Gaucher disease patients

Drugan

Caillaud

et al. 2017

Revista Romana De Medicina De Laborator

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Background: Gaucher disease (GD) is caused by a recessively inherited deficiency of glucocerebrosidase (recTL, recNciI, recA456P) were screened by DNA sequencing. Plasma chitotriosidase served as a biomarker of disease severity throughout the follow-up period. Results: 66 patients had the non-neuronopathic (type 1) form of GD and 3 had the chronic neuronopathic (type 3) phenotype. We identified 79% of the mutant alleles, among which the most frequent mutations were N370S (54%) and L444P (18%). We found a statistically significant (p<0.001) and moderate to good correlation between the total therapeutic dose and the residual chitotriosidase activity (R = 0.621). After two years of treatment, we noticed statistically significant variations in chitotriosidase activity corresponding to the most frequent genotypes (N370S/ unknown allele, N370S/L444P, N370S/N370S and N370S/R463Q).Conclusions: Allele distribution displayed specific features in Romanian GD patients, such as the high prevalence of the N370S allele. Chitotriosidase activity measurement allowed the investigation of genotype influence on treatment outcome.

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Section: Discussionsupporting

confidence: 56%

Laboratory diagnosis and follow-up of Romanian Gaucher disease patients

Drugan

Caillaud

et al. 2017

Revista Romana De Medicina De Laborator

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“…These mutations are N370S (c.1226A>G), L444P (c.1448T>C), 84insG (c.84dupG), and IVS2þ1G>A (c.115þ1G>A). Among non-Jewish patients, these mutations account for about 50-60 % of GD-associated mutations and there is a broad spectrum of other mutations (Grabowski and Horowitz 1997;Alfonso et al 2007). …”

Section: Introductionmentioning

confidence: 98%

Novel Mutations in the Glucocerebrosidase Gene of Brazilian Patients with Gaucher Disease

et al. 2012

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Gaucher disease (GD) is an autosomal recessive disorder resulting from glucocerebrosidase (GC) deficiency due to mutations in the gene (GBA) coding for this enzyme. We have developed a strategy for analyzing the entire GBA coding region and applied this strategy to 48 unrelated Brazilian patients with GD. We used long-range PCR, genotyping based on the Taqman® assay, nested PCR, and direct DNA sequencing to define changes in the gene. We report here seven novel mutations that are likely to be harmful: S125N (c.491G>A), F213L (c.756T>G), P245T (c.850C>A), W378C (c.1251G>C), D399H (c.1312G>C), 982-983insTGC (c.980_982dupTGC), and IVS10+1G>T (c.1505+1G>T). The last alteration was found as a complex allele together with a L461P mutation. We also identified 24 different mutations previously reported by others. G377S was the third most frequent mutation among the patients included in this study, after N370S and L444P. Therefore, this mutation needs be included in preliminary screens of Brazilian GD patients. The identification of mutant GBA alleles is crucial for increasing knowledge of the GBA mutation spectrum and for better understanding of the molecular basis of GD.

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“…Como alternativa terapéutica a la farmacológica en pacientes con enfermedad neurológica, puede plantearse el trasplante de médula ósea. No obstante, son pocos los pacientes que han recibido estos tratamientos, lo mismo que la terapia génica 39 , aún en etapa de experimentación.…”

Section: A R T í C U L O E S P E C I a Lunclassified

Enfermedad de Gaucher y su manejo clínico en el paciente pediátrico

et al. 2010

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RESUMENLa enfermedad de Gaucher constituye una enfermedad lisosomal hereditaria que tiene su origen en un defecto a nivel del gen que codifica el enzima betaglucosidasa ácida, cuya deficiencia condiciona la acumulación de glucocerebrósidos en los lisosomas de macrófagos, causando las manifestaciones clínicas del cuadro. En el niño la forma más frecuente es la tipo 2 o variante neuropática, caracterizada por la presencia de visceromegalias, trastornos hematológicos y alteraciones óseas estructurales. A menudo, presenta mal pronóstico, especialmente cuando sólo se disponía de la esplenectomía y trasplante de medula ósea como únicas terapias. Representa la primera enfermedad en la que se ha utilizado terapia enzimática sustitutiva demostrando su seguridad y eficacia durante la última década, permitiendo mejorar la calidad de vida de los pacientes y disminuyendo su morbimortalidad. El objetivo de este trabajo ha sido mostrar una revisión actualizada acerca de la fisiopatología, diagnóstico y manejo clínico-terapéutico de este complejo proceso. Palabras clave. Enfermedad de Gaucher, Niño. ABSTRACT Gaucher's disease and its clinical management in the pediatric patientGaucher disease is an inherited lysosomal disease whose origin lies in a defect at the level of the gene encoding the enzyme acid betaglucosidasa, which deficiency affects the accumulation of glucocerebroside in lysosomes of macrophages, causing the clinical manifestations of the table In children, the most common form is type 2 or neuropathic variant characterized by the presence of visceromegalies, hematological disorders and structural bone changes. Often presents a poor prognosis, especially when they were available splenectomy and bone marrow transplantation as the only therapies. It represents the first disease in which enzyme replacement therapy has been used to demonstrate safety and efficacy over the last decade, enabling improved patients' quality of life and decreasing their morbidity and mortality. The aim of this study was to show an updated review about the pathophysiology, diagnosis and clinical management -treatment of this complex process.

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Mutation analysis and genotype/phenotype relationships of Gaucher disease patients in Spain

Cited by 55 publications

References 14 publications

Laboratory diagnosis and follow-up of Romanian Gaucher disease patients

Laboratory diagnosis and follow-up of Romanian Gaucher disease patients

Novel Mutations in the Glucocerebrosidase Gene of Brazilian Patients with Gaucher Disease

Enfermedad de Gaucher y su manejo clínico en el paciente pediátrico

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