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

Siebert, Marina; Bock, Hugo; Michelin‐Tirelli, Kristiane; Coelho, Janice Carneiro; Giugliani, Roberto; Saraiva-Pereira, Maria Luiza

doi:10.1007/8904_2012_174

Cited by 18 publications

(14 citation statements)

References 21 publications

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“…This study also suggests that the presence of the N370S allele would be a protective factor for neurological manifestations. 15 Indeed, the only Type 3 GD patient presented the L444P allele, along with an unknown allele.…”

Section: Discussionmentioning

confidence: 98%

Study of enzyme replacement therapy for Gaucher Disease: comparative analysis of clinical and laboratory parameters at diagnosis and after two, five and ten years of treatment

Souza

Muniz

Brito

2014

Revista Brasileira de Hematologia e Hemoterapia

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ObjectiveTo evaluate the impact of enzyme replacement therapy for Gaucher Disease on clinical and laboratory parameters after two, five and ten years of treatment.MethodsData were collected from patient records and analyzed using BioEstat software (version 5.0). Student's t-test, Analysis of Variance (ANOVA), Wilcoxon test and Kruskal–Wallis test were used for statistical analysis. Hepatomegaly and splenomegaly were analyzed using the Kappa test.ResultsThere was a significant increase in hemoglobin levels (p-value <0.01) and platelet counts (p-value = 0.01) within two years of therapy. At the same time, the frequencies of splenomegaly (p-value <0.01) and hepatomegaly (p-value <0.05) reduced. These results were similar at five and ten years of enzyme replacement therapy.ConclusionsThere are substantial and quick (within two years) laboratory and clinical responses to enzyme replacement therapy. These improvements continue as long as enzyme replacement therapy is administered every two weeks, as recommended by the literature.

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Section: Discussionmentioning

confidence: 98%

Study of enzyme replacement therapy for Gaucher Disease: comparative analysis of clinical and laboratory parameters at diagnosis and after two, five and ten years of treatment

Souza

Muniz

Brito

2014

Revista Brasileira de Hematologia e Hemoterapia

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“…A mutation was considered “pathogenic” if it was previously reported in at least 1 patient with GD in the homozygous or compound heterozygous state or if it was predicted to have a clearly deleterious effect on function (e.g., frameshift or nonsense mutations). Previously published variants, such as E326K, which are not known to cause GD, were classified as polymorphisms.…”

Section: Methodsmentioning

confidence: 99%

GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease

et al. 2015

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Background Loss-of-function mutations in the GBA gene are associated with more severe cognitive impairment in PD, but the nature of these deficits is not well understood and whether common GBA polymorphisms influence cognitive performance in PD is not yet known. Objectives/Methods We screened the GBA coding region for mutations and the E326K polymorphism in 1,369 PD patients enrolled at 8 sites from the PD Cognitive Genetics Consortium. Participants underwent assessments of learning and memory (Hopkins Verbal Learning Test–Revised), working memory/executive function (Letter-Number Sequencing and Trail Making A and B), language processing (semantic and phonemic verbal fluency), visuospatial abilities (Benton Judgment of Line Orientation), and global cognitive function (Montreal Cognitive Assessment). We used linear regression to test for association between genotype and cognitive performance with adjustment for important covariates and accounted for multiple testing using Bonferroni corrections. Results Mutation carriers (n=60; 4.4%) and E326K carriers (n=65; 4.7%) had a higher prevalence of dementia (mutations, odds ratio =5.1; p=9.7 × 10−6; E326K, odds ratio =6.4; p=5.7 × 10−7) and lower performance on Letter-Number Sequencing (mutations, corrected p[pc]=9.0 × 10−4; E326K, pc=0.036), Trail Making B-A (mutations, pc=0.018; E326K, pc=0.018), and Benton Judgment of Line Orientation (mutations, pc=0.0045; E326K, pc=0.0013). Conclusions Both GBA mutations and E326K are associated with a distinct cognitive profile characterized by greater impairment in working memory/executive function and visuospatial abilities in PD patients. The discovery that E326K negatively impacts cognitive performance approximately doubles the proportion of PD patients we now recognize are at risk for more severe GBA-related cognitive deficits.

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“…The location of acid β-glucosidase gene is on chromosome 1q21. More than 350 different GBA mutations have been reported [12].…”

Section: Introductionmentioning

confidence: 99%

Twenty- five years of biochemical diagnosis of Gaucher disease: the Egyptian experience

Fateen

Abdallah

2019

Heliyon

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BackgroundGaucher disease is a rare multi-systemic metabolic disorder resulting from the deficiency of acid β-glucosidase activity, with consequent accumulation of glucocerebroside. Less than 15% of mean normal acid β-glucosidase activity in leukocytes is the gold standard for the diagnosis of Gaucher disease, and is generally supplemented by a massive elevation in chitotriosidase activity. We report here our experience in the biochemical diagnosis of Gaucher disease by showing the heterogeneity of the activity of enzymes over 25 years from 1993-2017, through the analysis of 5128 clinically suspected Gaucher disease cases referred to the Biochemical Genetics Department, National Research Centre, as the main reference lab in Egypt for the diagnosis of Inherited Metabolic Disorders.MethodsAcid β-glucosidase and chitotriosidase activities were measured in all referred cases. Sphinogmylinase activity was estimated for all cases with normal β-glucosidase activity and moderate elevation of chitotriosidase.ResultsOut of the 5128 suspected cases, 882 (17%) showed a deficiency in acid β-glucosidase activity, accompanied by a raised chitotriosidase activity, ranges (213-66700 umol/l/h) and mean (7255 umol/l/h). Deficient chitotriosidase activity was found in 9 patients (1%) with low β-glucosidase. 451 cases were diagnosed with acid sphingomyelinase deficiency patients (8.8%).ConclusionOther biochemical markers are needed in addition to chitotriosidase for the diagnosis and follow up. Molecular testing was done to a relatively small number but needs to be done to all diagnosed patients as many mutations are known to predict the course of the disease.

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

Cited by 18 publications

References 21 publications

Study of enzyme replacement therapy for Gaucher Disease: comparative analysis of clinical and laboratory parameters at diagnosis and after two, five and ten years of treatment

Study of enzyme replacement therapy for Gaucher Disease: comparative analysis of clinical and laboratory parameters at diagnosis and after two, five and ten years of treatment

GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease

Twenty- five years of biochemical diagnosis of Gaucher disease: the Egyptian experience

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