ArticleBlood2012
Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Value of Glucosylsphingosine (Lyso-Gb1) as a Biomarker in Gaucher Disease: A Systematic Literature Review.International journal of molecular sciences · 2020Pooled it
- Integrating Gaucher disease (GD) into mainstream hematological curriculum training.HemaSphere · 2026Article
- Precision genomic profiling in Gaucher disease: insights from atypical presentations.Frontiers in genetics · 2025Article
- Case Report: A patient with lynch syndrome with vaginal endometriosis-associated malignancy and synchronous colonic tubulovillous adenoma.Frontiers in medicine · 2025Article
- Infiltration of Apoptotic M2 Macrophage Subpopulation Is Negatively Correlated with the Immunotherapy Response in Colorectal Cancer.International journal of molecular sciences · 2022Article
- Hematological Findings in Lysosomal Storage Disorders: A Perspective from the Medical Laboratory.EJIFCC · 2022Article
- Novel Management and Screening Approaches for Haematological Complications of Gaucher's Disease.Journal of blood medicine · 2021Review
- Targeted sequencing of genes associated with the mismatch repair pathway in patients with endometrial cancer.PloS one · 2020Article
- Exploring genetic modifiers of Gaucher disease: The next horizon.Human mutation · 2018Review
- Gaucher disease and chronic myeloid leukemia: first reported patient receiving enzyme replacement and tyrosine kinase inhibitor therapies simultaneously.Clinical case reports · 2018Article
- A Next Generation Multiscale View of Inborn Errors of Metabolism.Cell metabolism · 2016Review
- Evaluation of disease burden and response to treatment in adults with type 1 Gaucher disease using a validated disease severity scoring system (DS3).Orphanet journal of rare diseases · 2015Article
- Lysosomal diseases: diagnostic update.Journal of inherited metabolic disease · 2014Review
- Patients with type 1 Gaucher disease in South Florida, USA: demographics, genotypes, disease severity and treatment outcomes.Orphanet journal of rare diseases · 2014Article
- Gaucher disease and malignancy: a model for cancer pathogenesis in an inborn error of metabolism.Critical reviews in oncogenesis · 2013Review
- Disease-drug pairs revealed by computational genomic connectivity mapping on GBA1 deficient, Gaucher disease mice.Biochemical and biophysical research communications · 2012Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Gaucher disease (GD), an inherited macrophage glycosphingolipidosis, manifests with an extraordinary variety of phenotypes that show imperfect correlation with mutations in the GBA gene. In addition to the classic manifestations, patients suffer from increased susceptibility to hematologic and nonhematologic malignancies. The mechanism(s) underlying malignancy in GD is not known, but is postulated to be secondary to macrophage dysfunction and immune dysregulation arising from lysosomal accumulation of glucocerebroside. However, there is weak correlation between GD/cancer phenotype and the systemic burden of glucocerebroside-laden macrophages. Therefore, we hypothesized that genetic modifier(s) may underlie the GD/cancer phenotype. In the present study, the genetic basis of GD/T-cell acute lymphoblastic lymphoma in 2 affected siblings was deciphered through genomic analysis. GBA gene sequencing revealed homozygosity for a novel mutation, D137N. Whole-exome capture and massively parallel sequencing combined with homozygosity mapping identified a homozygous novel mutation in the MSH6 gene that leads to constitutional mismatch repair deficiency syndrome and increased cancer risk. Enzyme studies demonstrated that the D137N mutation in GBA is a pathogenic mutation, and immunohistochemistry confirmed the absence of the MSH6 protein. Therefore, precise phenotype annotation followed by individual genome analysis has the potential to identify genetic modifiers of GD, facilitate personalized management, and provide novel insights into disease pathophysiology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.